Lung function, symptoms and inflammation during exacerbations of non-cystic fibrosis bronchiectasis: a prospective observational cohort study.

Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described

Abnormal recovery and recurrence of chronic obstructive pulmonary disease exacerbations

This thesis examines chronic obstructive pulmonary disease (COPD) exacerbation recovery in depth. This is an important topic to study since prolonged recovery and recurrence are common, severe and poorly understood events. The methodology involved patient reported outcome (PRO) tools and objective cough monitoring to examine symptomatic changes during exacerbations, and also the measurement of systemic and airway biomarkers during COPD exacerbations to identify patients at risk of non-recovery and recurrence. Finally, this thesis also included a randomised placebocontrolled trial to investigate if Roflumilast can improve exacerbation recovery. This thesis showed that PROs provide reliable measurements of exacerbation severity. Furthermore, cough frequency increased acutely from baseline levels at exacerbation and fell during subsequent recovery. The biomarker work demonstrated that increased systemic inflammation at exacerbation onset predicts non-recovery and that faster resolution of neutrophilic inflammation is associated with shorter recovery. Roflumilast did not accelerate reduction of sputum neutrophils from exacerbation onset to 2 weeks post exacerbation, but did improve lung function recovery when given on top of standard therapy. This thesis demonstrates that PROs can be used in clinical practice to evaluate exacerbation recovery, and in trials of acute exacerbation therapies. It also provides evidence that targeting inflammation may improve recovery time. Future research should seek to define the use of Roflumilast as part of a personalised strategy that treats patients according to exacerbation phenotype

Aspects of Discrete Breathers and New Directions

We describe results concerning the existence proofs of Discrete Breathers (DBs) in the two classes of dynamical systems with optical linear phonons and with acoustic linear phonons. A standard approach is by continuation of DBs from an anticontinuous limit. A new approach, which is purely variational, is presented. We also review some numerical results on intraband DBs in random nonlinear systems. Some non-conventional physical applications of DBs are suggested. One of them is understanding slow relaxation properties of glassy materials. Another one concerns energy focusing and transport in biomolecules by targeted energy transfer of DBs. A similar theory could be used for describing targeted charge transfer of nonlinear electrons (polarons) and, more generally, for targeted transfer of several excitations (e.g. Davydov soliton).Comment: to appear in the Proceedings of NATO Advanced Research Workshop "Nonlinearity and Disorder: Theory and Applications", Tashkent,Uzbekistan,October 1-6, 200

Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST)

BACKGROUND: Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. METHODS: Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12\u2009months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. RESULTS: Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r =\u20090.61, p =\u20090.0037, Leicester Cough Questionnaire, r =\u2009-\u20090.52,p =\u20090.0015, St Georges Respiratory Questionnaire, r =\u20090.61,p <\u20090.0001 and 6\u2009min walk test, r =\u2009-\u20090.46,p =\u20090.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3\u2009days (SD 5.7). A minimum clinically important difference of 4 points is proposed. CONCLUSIONS: The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials

Daily activity during stability and exacerbation of chronic obstructive pulmonary disease

BACKGROUND: During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. METHODS: Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. RESULTS: The 73 COPD patients (88% male) had a mean (+/-SD) age 71(+/-8) years and FEV1 53(+/-16)% predicted. They recorded pedometer data on a median 198 days (IQR 134-353). At exacerbation onset, symptom count rose by 1.9(+/-1.3) and PEF fell by 7(+/-13) l/min. Mean daily step count fell from 4154(+/-2586) steps/day during a preceding baseline week to 3673(+/-2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = -0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). CONCLUSIONS: COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time

Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease

There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort

The origin of defects induced in ultra-pure germanium by Electron Beam Deposition

The creation of point defects in the crystal lattices of various semiconductors by subthreshold events has been reported on by a number of groups. These observations have been made in great detail using sensitive electrical techniques but there is still much that needs to be clarified. Experiments using Ge and Si were performed that demonstrate that energetic particles, the products of collisions in the electron beam, were responsible for the majority of electron-beam deposition (EBD) induced defects in a two-step energy transfer process. Lowering the number of collisions of these energetic particles with the semiconductor during metal deposition was accomplished using a combination of static shields and superior vacuum resulting in devices with defect concentrations lower than $10^{11}\,$cm$^{-3}$, the measurement limit of our deep level transient spectroscopy (DLTS) system. High energy electrons and photons that samples are typically exposed to were not influenced by the shields as most of these particles originate at the metal target thus eliminating these particles as possible damage causing agents. It remains unclear how packets of energy that can sometimes be as small of 2eV travel up to a $\mu$m into the material while still retaining enough energy, that is, in the order of 1eV, to cause changes in the crystal. The manipulation of this defect causing phenomenon may hold the key to developing defect free material for future applications.Comment: 18 pages, 9 figure

Effect of spirometry on intra-thoracic pressures

Due to the high intra-thoracic pressures associated with forced vital capacity manoeuvres, spirometry is contraindicated for vulnerable patients. However, the typical pressure response to spirometry has not been reported. Eight healthy, recreationally-active men performed spirometry while oesophageal pressure was recorded using a latex balloon-tipped catheter. Peak oesophageal pressure during inspiration was - 47 ± 9 cmH O (37 ± 10% of maximal inspiratory pressure), while peak oesophageal pressure during forced expiration was 102 ± 34 cmH O (75 ± 17% of maximal expiratory pressure). The deleterious consequences of spirometry might be associated with intra-thoracic pressures that approach maximal values during forced expiration

Clinical and Imaging Characteristics of Arteriopathy Subtypes in Children with Arterial Ischemic Stroke: Results of the VIPS Study.

Background and purposeChildhood arteriopathies are rare but heterogenous, and difficult to diagnose and classify, especially by nonexperts. We quantified clinical and imaging characteristics associated with childhood arteriopathy subtypes to facilitate their diagnosis and classification in research and clinical settings.Materials and methodsThe Vascular Effects of Infection in Pediatric Stroke (VIPS) study prospectively enrolled 355 children with arterial ischemic stroke (2010-2014). A central team of experts reviewed all data to diagnose childhood arteriopathy and classify subtypes, including arterial dissection and focal cerebral arteriopathy-inflammatory type, which includes transient cerebral arteriopathy, Moyamoya disease, and diffuse/multifocal vasculitis. Only children whose stroke etiology could be conclusively diagnosed were included in these analyses. We constructed logistic regression models to identify characteristics associated with each arteriopathy subtype.ResultsAmong 127 children with definite arteriopathy, the arteriopathy subtype could not be classified in 18 (14%). Moyamoya disease (n = 34) occurred mostly in children younger than 8 years of age; focal cerebral arteriopathy-inflammatory type (n = 25), in children 8-15 years of age; and dissection (n = 26), at all ages. Vertigo at stroke presentation was common in dissection. Dissection affected the cervical arteries, while Moyamoya disease involved the supraclinoid internal carotid arteries. A banded appearance of the M1 segment of the middle cerebral artery was pathognomonic of focal cerebral arteriopathy-inflammatory type but was present in &lt;25% of patients with focal cerebral arteriopathy-inflammatory type; a small lenticulostriate distribution infarct was a more common predictor of focal cerebral arteriopathy-inflammatory type, present in 76%. It remained difficult to distinguish focal cerebral arteriopathy-inflammatory type from intracranial dissection of the anterior circulation. We observed only secondary forms of diffuse/multifocal vasculitis, mostly due to meningitis.ConclusionsChildhood arteriopathy subtypes have some typical features that aid diagnosis. Better imaging methods, including vessel wall imaging, are needed for improved classification of focal cerebral arteriopathy of childhood