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No description available.

Thesis (Ph. D.)--University of Montana, 2007. / Title from title screen. Description based on contents viewed July 24, 2007. Includes bibliographical references (p. 154-161).

The use of exercise is a valuable tool in the healthcare management of young patients with chronic chest diseases (CCD). Indeed, exercise testing yields important prognostic data which are a strong predictor of survival. Such information can indicate to the clinician to increase drug therapy treatment, and functional capacity of the patient can be monitored over time with repeated testing. Exercise training has been shown to improve both aerobic and anaerobic fitness and quality of life in patients with lung disease. The use of exercise testing and training in the healthcare of patients with lung disease in the UK, however, has not been investigated. In order for recommendations for exercise testing and training based on scientific evidence to be implemented, they should relate to current standards and resources. Therefore, the first study of the present thesis sought to characterise the use of both exercise testing and training in UK Cystic fibrosis (CF) clinics through a nationwide audit. Data from the audit showed that exercise testing and training are underused despite recognition of the importance of each in the healthcare of the patient by clinicians and other healthcare providers. Indeed, resources for exercise testing in UK CF clinics are limited. A patient over the age of 8 y will only have a 41.1 % chance of receiving an exercise test of any type over a 12 month period, and the exercise test will be quite crude. Exercise training is frequently discussed with the patient; however, there is a strong likelihood (72.9 %) that the advice given will only be general encouragement. The prognostic value of exercise testing is becoming increasingly recognised. Indeed, peak oxygen uptake (VO2peak) derived through maximal cardiopulmonary exercise testing (CPET) has been reported to be equal or superior to that of resting spirometric lung function tests in the prognostic evaluation of patients with CCD. Furthermore, a high correlation between VO2peak and long term survival in both adults and children with CF has been reported. Other physiological data from CPET, such as oxygen uptake (VO2) recovery following CPET, has not been investigated in young patients with CCD and may provide an additional physiological marker of patient health. The aim of study two, therefore, was to investigate recovery following CPET in young patients with CCD, and determine if any significant relationships exist between VO2 recovery and measures of disease severity in these patients. Data from study two showed that young patients with CCD compared to healthy controls had significantly reduced aerobic fitness (t52 = - 2.64, P = 0.011), and the fast component of the VO2 recovery following CPET, analysed by a mono-exponential model, is significantly prolonged (t52 = 2.63, P = 0.011). Furthermore, the fast component of the VO2 recovery is significantly related to disease severity, as assessed by the Shwachman score (SS), in the CF subgroup (r = - 0.75, P < 0.001), and as assessed by forced expiratory volume in 1 s (FEV1), in the young patients with CCD (r = - 0.49, P = 0.009). Thus, indicating that greater disease severity is associated with a longer VO2 recovery following CPET. A significant relationship between VO2peak and VO2 recovery was shown in the young patients with CCD (r = - 0.45, P = 0.018). Although the relationship is significant, however, it is still quite weak, and, therefore, indicates that the VO2 recovery is not closely related to the VO2peak in these patients. Quality of life and likelihood of survival are greater in patients with CCD with higher levels of aerobic fitness, and regular exercise has been shown to improve both lung function and exercise capacity in these patients. Indeed, exercise training programmes tailored to the individual patient are recommended in the standards of patient healthcare in the UK. Whilst the chronic effects of regular exercise have been investigated, the acute physiological responses to exercise training have not been studied in young patients with CCD. In study three young patients with CCD and healthy controls performed intermittent exercise (IE) designed to replicate the typical activity and exercise patterns of young people. Following IE, in the healthy controls the VO2 required to sustain moderate steady-state exercise fell significantly from 3 min to 1 h and 1 h to 24 h, however, in the young patients with CCD VO2 during moderate steady-state exercise increased significantly from 3 min to 1 h and then decreased significantly from 1 h to 24 h (main effect for time: F1.5,79.2 = 22.82, P < 0.001). A significant time × group interaction between young patients with CCD and controls in VO2 during moderate steady-state exercise 3 min, 1 h and 24 h following IE (interaction: F1.5,79.4 = 30.01, P < 0.001) may suggest that metabolic stress is still evident over this time period, which may be indicative of fatigue. Data from the present thesis shows that exercise is underused in UK CF clinics, with the availability of equipment and personnel both being limiting factors. Furthermore, a lack of standardisation in the provision of exercise between clinics is evident. In studies two and three, data shows different physiological responses following CPET and IE, respectively, between children with CCD and controls. The present thesis has advanced our understanding of the provision of exercise in the healthcare of CF in the UK, and furthered knowledge in how young patients with CCD respond physiologically to exercise.

PhD, Faculty of health Sciences, University of the Witwatersrand, 2000

The purpose of this study was to examine the relationships between inflammation, infection and lung function in cystic fibrosis during the evolution of lung disease in childhood and early adolescence. The developmental stages of childhood and the progression of lung disease together affected the methods and techniques used in the study, with the consequence that the work for this thesis fell naturally into two parts. The first part concerned the study of early lung disease in infants and young children who were unable to expectorate or to cooperate with lung function testing. In the second part, the inflammatory processes in both stable lung disease and during clinical exacerbations in older children and adolescents were studied non-invasively using sputum. The absence of a recognised definition of pulmonary exacerbation lead to further investigation into clinical heterogeneity in the diagnosis and management of an exacerbation. In early lung disease, inflammation was not found to be independent of infection, with pathogens in the lower airways found to correlate with levels of inflammation, respiratory system compliance and degree of air trapping (a relationship not previously shown). This suggested that infection remains the key target to minimizing lung damage in cystic fibrosis. The relationship between sputum markers of inflammation and lung pathology in established disease was found to be less clear, with high inflammation levels in both stability and during exacerbation. Reduction in sputum inflammatory levels following treatment of an exacerbation was found to be greater in those with lower pre-treatment levels. The definition and management of an exacerbation was found to be an area lacking consensus among clinicians, with likely consequent heterogeneity of clinical care and therefore inhomogeneity of hospitalization as a surrogate measure of exacerbation in a research setting. The work from this thesis, and the ensuing publications, has contributed to the understanding of the interactions between the inflammatory and infectious processes involved in CF lungdisease, in both early and more established lung disease in childhood.

Since the first modern investigations into Egyptian mummies in the 1970s, anthracosis and silicosis have regularly been found in mummified lungs (Tapp, 1975; Walker et al, 1987). Anthracosis, lung irritation caused by carbon particles, is well researched in modern populations but very little is known about the disease in ancient times. Similarly, little is known about the prevalence of silicosis, caused by the inhalation of particles of silicon, in ancient times. It has been assumed that carbon was inhaled through the combustion of fuel for cooking and illumination whilst silicon came from the desert environment.This study aims to test these assumptions by characterising the shape, size and elemental composition of the organic and inorganic particles contained within ancient lung tissue. When these particles are compared against surrogate carbon and silicon particles, it may be possible to identify them and reveal their aetiology.Surrogate carbon particles were produced through controlled combustion of fuels the ancient Egyptians are likely to have used. The modern silica containing sand was collected from various archaeological sites in Egypt. A sonication method was used to extract particles from ancient tissue. After extraction, individual ancient particles were isolated and examined for size and shape analysis using light microscopy. The surrogate particles were examined in the same manner. The particles were then imaged using environmental scanning electron microscopy (ESEM) and elemental profiles determined by energy dispersive X-ray analysis (EDAX). Bulk analysis by mass spectrometry was then employed to qualitatively and quantitatively analyse the elements contained within ancient lung particles and the modern surrogates. Electron probe micro-analysis (EPMA) was used to map the deposition and elemental composition of inorganic compounds in sections of ancient lung. Further information on the bonds and chain length of soots were obtained through FTIR and Raman spectroscopy.Results have shown the presence of anthracosis and birefringent particles in all ancient lung tissues examined by this study. Both organic and inorganic ancient particles have been found to be respirable (ie, less than 10 microns in diameter) and were present in the lung pre-mortem. EDX and ICP-MS results show the inorganic particles to consist of aluminium silicates (sand) and calcium carbonate (limestone). FTIR and Raman spectroscopy were not accurate enough to detect the ancient or surrogate soot bonds and were not suited to this study.

Sarcoidosis is a multisystem inflammatory disorder of unknown aetiology. The immune pathology is characterised by dysregulated T cell (T_H1) activity, macrophage activation and granuloma formation, resulting in systemic inflammation, and organ dysfunction. I hypothesised that, as the systemic precursor to the macrophage, altered monocyte activity in sarcoidosis may contribute to the early immune pathology of the disease. In this thesis, I examined their phenotype, four key monocytic functions: cytokine production, suppression of T cell proliferation, phagocytosis and fusion (as a precursor to granulomagenesis); and their gene expression profile compared to monocytes from healthy controls. My data show that the expanded monocyte compartment comprise a greater proportion of the inflammatory (CD14⁺⁺CD16⁺) and patrolling (CD14⁺CD16⁺⁺) subsets, increased TNFα and IL-12 and decreased IL-10 and IL-4 production in sarcoidosis compared with healthy controls. The IL-10 deficit renders the monocytes less able to regulate T cell proliferation or their own fusion to multinucleate giant cells, potentially contributing to T cell expansion and granuloma formation respectively. Additionally, sarcoidosis monocytes are less able to phagocytose inert material. I also showed that previously reported deficiency in invariant NKT cells and low serum vitamin D levels in sarcoidosis may be linked to reduced IL-10 production by monocytes. Vitamin D treatment in vitro restored most of these deficiencies and provides a potential therapeutic method for manipulating monocyte function and disease genesis in sarcoidosis.

The purpose of this study was to compare power output and ventilatory measurements between the steep ramp test (SR) and both the 30-second Wingate anaerobic (WAT) and standard cardiopulmonary exercise tests (CPET) in chronic obstructive pulmonary disease (COPD). 11 patients (7 males and 4 females) underwent spirometry, a CPET, WAT and SR test. Repeated measures ANOVA was used to compare the differences between the peak work rate of the CPET (CPET_peak), SR (SR_peak), and the average power of the WAT (W_avg). The W_avg was higher than the SR_peak, which was higher than the CPET (231.2 ± 113.4, 156.8 ± 67.9, 65.9 ± 35.9, p>0.05 respectively). There were no differences found between the tests at end-exercise for inspiratory reserve volume (IRV), ventilation (V_E), and end-expiratory lung volume (EELV). Tidal volume (V_T) was also compared between the tests as a percentage of the inspiratory capacity (IC) remaining at end-exercise and no differences were found. The similarity between the ventilatory measures indicates a similar level of constraint, despite the large difference in work rates achieved, in all 3 tests. This shows that a standard CPET underestimates leg power in COPD patients, and the WAT and SR may be better indicators of leg muscle power and anaerobic type exercise.