The goal of this dissertation was to assess the impact of the stable environment on the breathlessness of horses. Breathlessness is a lay term for COPD, i.e. Chronic obstructive pulmonary disease. The anatomy and physiology of respiration of horses and the COPD are concisely described in this dissertation. The dissertation also deals with preventive measures taken in stables and the basic parameters and the microclimate of stables. The measurements were carried out in each season of the year over a period of one years. The measurements took place in 8 stables and were carried out on 16 horses, 8 of whom were healthy and the other 8 were suffering from COPD. The horses breath, pulse and temperature were measured at different levels of physical aktivity. The microclimate of each stable was also measured. The results were statistically evaluated and verbally commented on the knowledge gained from literature searches.

Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease characterized by progressive and irreversible airway obstruction, and mainly caused by a chronic exposure to lung irritants. As of 2010, 384 million people suffered from COPD worldwide. It is widely accepted that a chronic inflammatory response is integral to COPD pathogenesis and linked to disease progression. The cellular mediators and molecular mechanisms of COPD-associated inflammation are not completely understood and are difficult to emulate in animal models, which hinders the development of better treatments. In this study, experimental COPD and its associated inflammation were induced in mice using a 4-week protocol involving intranasal administration of LPS and elastase. Model validation on wild-type mice yielded COPD-like disease judging from flow cytometric analyses with and pulmonary function testing. After 4 weeks of exposure to LPS and elastase, mice developed classic aspects of COPD such an increase in lung-infiltrating cells, (e.g. neutrophils, CD4+and CD8+ T-cells). Acute inflammation in the form of substantial neutrophilia was due to the last LPS administration, whereas the observed eosinophilia and elevated counts of mast cell populations, CD4+ and CD8+ T-cells were due to the cumulative effects of LPS and elastase. The nature of COPD-associated inflammation in mast cell deficient mice was investigated in two experiments. Our first experiment suggested a mild protective role of mast cells, a finding not reproduced in the second experiment possibly due to expired elastase. Our study suggests that mast cells are not required for COPD-associated inflammation.

No description available.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease comprising of respiratory-related and systemic effects, including impairments in balance. Balance impairments are especially problematic as they increase the risk of falling, potentially leading to negative outcomes such as hospitalization, disability, and death. The main objectives of this thesis were to 1. determine underlying balance impairments that distinguish between individuals with COPD with and without a history of falls and 2. explore facilitators and barriers of a home-based fall prevention program for people with COPD. The first study of this thesis was a secondary analysis of cross-sectional data that showed that the stability limits/verticality and postural responses subcomponents of the Balance Evaluation Systems Test (BESTest) distinguished between those with and without a fall history among 72 patients with moderate to severe COPD. The stability limits/verticality subcomponent also showed acceptable accuracy in identifying individuals with COPD at high risk of falls (cut-off score of 73.8%). In the second study, a qualitative analysis of interviews with 15 patients who completed a home-based fall prevention program, participants indicated that programs that are personalized and focus on providing support for older adults with COPD may help to improve adherence and reduce participants’ risk of falling. The findings from the two studies included in this thesis provide new knowledge for informing fall risk assessment and prevention for people with COPD. / Thesis / Master of Science (MSc)

Aerosolized bronchodilator drugs are commonly used for treatment of horses with chronic obstructive pulmonary disease. Relative efficacy of sympathomimetic and parasympatholytic bronchodilators for relief of acute airway obstruction and improvement of pulmonary gas exchange was compared in 6 horses with COPD. Physical examination, arterial and venous blood gas analysis and measurement of end-tidal CO₂ tension were performed at time zero, 30 minutes, 1, 2, 3 and 4 hours after administration of aerosol ipratropium (0.35 μg/kg), albuterol (1 μg/kg) or placebo via an equine Aeromask and metered dose inhaler. Physiologic shunt fraction (QS/QT), alveolar dead space fraction (VD/VT) and alveolar to arterial oxygen tension difference (p(A-a)O₂) were calculated using standard formulas. At time zero, horses demonstrated severe respiratory compromise and marked alterations in pulmonary gas exchange, indicative of alveolar hypoventilation, VA/Q mismatching and diffusion impairment. Ipratropium treatment significantly (p< 0.05) reduced arterial CO₂ tension and end-tidal CO₂ tension toward normal, but significantly increased p(A-a)O₂ from baseline. The change in paCO₂ after ipratropium treatment was significantly different from albuterol and placebo treatment groups. There were no significant changes in response variables after albuterol and there were no treatment by time interactions. These results indicate that, under the conditions of this study, ipratropium (0.35 μg/kg) improved alveolar ventilation and had superior bronchodilator efficacy than albuterol (1 μg/kg) in horses with severe COPD. Marked impairment of pulmonary gas exchange persisted after bronchodilators, emphasizing that anti-inflammatory therapy and environmental control are also necessary for effective treatment of severe equine COPD. / Master of Science

No / The challenges associated with patient-based research in palliative care are well documented. This paper focuses on the ethical challenges and discusses them in the context of a pilot study to explore the palliative-care needs of patients with moderate and severe chronic obstructive pulmonary disease. The main ethical challenge encountered related to problems surrounding the use of terminology, specifically the terms ‘palliative care’ and ‘chronic obstructive pulmonary disease’. The approving ethics committee specified that these terms be removed from all patient materials in order to protect patients from undue distress. The impact of this ethical advice on patients’ ability to give fully informed consent is discussed. This paper highlights a requirement for appropriately resourced and well-managed studies in palliative care, and identifies a need for the development of appropriate strategies in order to ensure the informed participation of patients with non-cancer diagnoses in palliative-care research.

Acute exacerbation of chronic obstructive pulmonary disease (COPD) is one of the leading causes of hospital readmissions within 30 days. Frequent readmissions negatively affect hospital reimbursements and patient outcomes. Creative strategies, such as COPD care bundles, have been shown to reduce readmission rates according to existing studies. A COPD discharge bundle was developed and implemented at 1 community hospital in response to an identified problem with COPD readmissions. Evaluation of this quality improvement initiative was the purpose of this project study. The practice-focused question was: Have 30-day readmission rates changed following the implementation of a COPD discharge bundle prior to transitioning from hospital to home? The framework selected for this project was the model for improvement. Sources of evidence included existing hospital data to evaluate the change in readmissions. The chi-square test of independence was used to assess the difference in frequency of 30-day readmissions. Pre and post-bundle implementation comparisons of readmission rates showed a decrease for 3 out of the 4 groups compared; these results were not statistically significant. Analysis of the post-bundle intervention groups revealed lower 30-day readmissions for individuals who were bundle compliant versus noncompliant and for those who spoke with a pharmacist within 48 hours of discharge opposed to those who did not; these results were statistically significant. Continued use of the bundle and maintaining the role of the pharmacist was recommended. Reduction of readmissions within 30-days has positive social implications for hospitals through financial gains and for the COPD population by improving overall health outcomes.

No description available.

There is considerable evidence that cigarette smoking is the primary etiology of chronic obstructive pulmonary disease (COPD), and that oxidative stress occurs in COPD with the family of tissue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzymes playing a significant role in lung pathogenesis. The purpose of this study was to determine the effects of cigarette smoke extract (CSE) on Nox signaling to epithelial sodium channels (ENaCs). Pre-treatment with diphenyleneiodonium (DPI), a pan-Nox inhibitor, prevented stimulatory effects of CSE on ENaC activity; open probability (Po) changed from 0.36 +/- 0.09 to 0.11 +/- 0.02; n=10, p=0.01 following CSE and DPI exposure. Likewise, Fulvene-5 (which inhibits Nox2 and Nox4 isoforms) decreased the number of ENaC per patch (from 2.75 +/- 0.25 to 1 +/- 0.5, n=9, p=0.002) and open probability (0.18 +/- 0.08 to 0.02 +/- 0.08, p=0.04). Cycloheximide chase assays show that CSE exposure prevented alpha-ENaC subunit degradation, whereas concurrent CSE exposure in the presence of Nox inhibitor, Fulvene 5, resulted in normal proteolytic degradation of alpha-ENaC protein in primary isolated lung cells. In vivo, co-instillation of CSE and Nox inhibitor promoted alveolar flooding in C57Bl6 mice compared to accelerated rates of fluid clearance observed in CSE alone instilled lungs. Real-time PCR indicates that mRNA levels of Nox2 were unaffected by CSE treatment while Nox4 transcript levels significantly increased 3.5 fold in response to CSE. Data indicate that CSE is an agonist of Nox4 enzymatic activity, and that CSE-mediated Nox4 plays an important role in altering lung ENaC activity.

Aim The overall objective of this thesis was to increase the knowledge and validate methods for assessment of total daily energy expenditure (TEE), energy requirement and energy intake (EI) in women with COPD. We also investigated the relationship of BMI with clinical characteristics of COPD in a population-based study. Due to the substantial and increasing morbidity in women with COPD, special attention was given to this group. Methods Resting metabolic rate (RMR) was measured by indirect calorimetry (IC). TEE was measured by criterion method, doubly labeled water (DLW) (Paper I-III) during a 14-day period. TEE was simultaneously assessed by SenseWear Armband, software version 5.1 and 6.1 (SWA5 respectively SWA6), and ActiHeart (paper I). EI was assessed by diet history interview and 7-day food diary (paper II), and energy requirement was predicted using pedometer-determined physical activity level (paper III). Energy requirement data was also acquired from studies concerning TEE measured by DLW in patients with COPD (paper IV). BMI and other characteristics in subjects with COPD were compared with non-COPD subjects in a population-based study, Obstructive Lung disease in Norrbotten study (OLIN) (paper V). Results There was a large variation in RMR and TEE measured by DLW in this group of women with COPD. The results of energy expenditure study showed that the SWA5 assessed TEE with good accuracy over a 14-day period in free-living women with COPD. However, the SWA6 and ActiHeart methods tend to underestimate TEE. A higher proportion of women were within ± 5% of the TEE individually measured with the DLW method using SWA5 than SWA6 and AH (63%, 47%, 37% respectively). The agreement between the TEE measured by DLW and SWA5 was strong, and with SWA6 and ActiHeart it was lesser. Bland-Altman plots revealed no systematic bias for TEE. The reported EI was underestimated by 28% respectively 20 % when assessed by diet, and the 7-day food diary compared with the criterion method, DLW. More women were identified as valid-reporters based on their 7- day food diaries than on their diet histories (63% vs 32%). The accuracy of reported EI was only related to BMI. The agreement between the DLW and the EI methods was weak. The Bland-Altman plots revealed a slight systematic bias for both methods. The energy requirement predicted by pedometer-determined PAL multiplied by six different RMR equations was within a reasonable accuracy (±10%) of the measured TEE for all equations except one. The agreement between the DLW and four of six predicted TEE methods was strong. The Bland– Altman plots revealed no systematic bias for predicted energy requirement except for one. Estimated PAL from the pedometer was lower by 14 % than the measured criterion PAL. The energy requirement calculation based on available TEE data measured by DLW varied by BW and FFM. Compared to men, women had a lower RMR and TEE/kg BW/day, and higher RMR and TEE/kg FFM/day. The correlates of RMR/kg BW were gender and forced expiratory volume in 1st second (FEV1) % of predicted value, of TEE/ kg BW the correlates were age and gender, and of TEE/kg FFM were age and FEV1 % predicted. BMI decreased significantly with increase in disease severity and correlated significantly to forced expiratory volume in 1st second % predicted. In the population-based study (OLIN), subjects with COPD had lower BMI and a higher prevalence of underweight than in non-COPD, and its sub-groups namely, normal lung function and restrictive spirometry pattern subjects. There was an independent association between COPD and low BMI. Fewer COPD subjects were obese than in the non-COPD, normal lung function and restrictive spirometry pattern groups. Among the subjects with COPD, women had a lower mean BMI and a higher proportion were under-weight than men. In COPD women with under-weight, FEV1 % predicted values increased with an increase in BMI. Conclusion Compared with the gold standard DLW method, the total daily energy expenditure can be assessed reliably by SenseWear Armband 5 in women with COPD, while other devices underestimated TEE. The energy intake was underestimated by diet history and 7-day food diary methods, and energy requirement was predicted with reasonable accuracy using pedometer-determined PAL and common RMR equations, compared with DLW. Furthermore, the energy requirement was determined per kg BW/day and per kg FFM/day, using DLW based TEE data in patients with COPD. In the population-based study (OLIN), subjects with COPD had lower BMI and higher prevalence of under-weight than subjects without COPD. There was a gender difference, which was particularly significant in COPD, for women to have lower mean BMI and a higher prevalence of under-weight. The present findings indicate that low BMI is common in COPD and needs to be intervened. For a successful nutritional treatment, it is imperative to assess the patient’s ener / Bakgrund/Syfte Kroniskt obstruktiv lungsjukdom (KOL) är en av de stora folksjukdomarna där dödligheten ökar mest globalt sett. I Sverige är ökningen av KOL mest uttalad för kvinnor. Viktminskning är vanligt vid KOL. Låg kroppsvikt, låg andel fettfrimassa och lågt kroppsmasseindex (BMI) är dessutom riskfaktorer för ökad sjuklighet och dödlighet. Det finns därför behov av att ge anpassad kostbehandling for att motverka viktnedgång eller för att uppnå viktuppgång. För framgångsrik kostbehandlingen behövs metoder som på ett tillförlitligt sätt kan bedöma den totala energiförbrukningen, energiintag, och energibehov., Dessa metoder har ännu inte utvärderats väl hos KOL patienter. Det övergripande syftet därför med denna avhandling var att validera och öka kunskaperna om metoder som är tillförlitliga för att kunna bedöma energiförbrukning, energiintag och energibehov hos patienter med KOL. Vidare, jämfördes BMI och kliniska egenskaper mellan personer med och utan KOL in en populations-baserad studie. Metoder Viloenergiförbrukning mättes med indirekt kalorimeter hos kvinnor med KOL. Den totala energiförbrukningen mättes hos dessa kvinnor med dubbelmärktvatten metoden (DLW) (Arbete 1-3) under en 14-dagars period. Samtidigt bedömdes energiförbrukningen med två aktivitetesmätare, SenseWear Armband, mjukvaruversion 5.1 och 6.1 (SWA5 respektive SWA6), och ActiHeart (arbete 1). Energiintaget bedömdes med kostanamnes och 7-dagars matdagbok (arbete 2); energibehovet beräknades med olika viloenergiförbruknings formler och fysisk aktivitetsnivå uppskattad med en stegräknare (arbete 3). En sammanställning och en analys genomfördes av energibehovet baserad på data från flera studier som har mätt TEE med DLW hos KOL patienter (Arbete 4). BMI och kliniska egenskaper jämfördes mellan personer med och utan KOL i ett stort populationsbaserat material från Obstruktiv Lungsjukdom i Norrbotten (OLIN) studien (Arbete 5). Resultat Det fanns en stor variation in viloenergiförbrukningen och energiförbrukning mätt med DLW hos kvinnor med KOL. Energiförbrukningen mätt med aktivitetsmätare SWA5 visade hög tillförlitlighet både på grupp- och individnivå, medan SWA6 och ActiHeart metoderna underskattade energiförbrukningen. Energiintaget bedömd med kostanamnes och 7-dagars matdagbok visade en underskattning med 28% respektive 20% jämfört med DLW metoden. Det rapporterade energiintaget stämde för flertalet kvinnor bättre mot DLW metoden när energiintaget bedömdes med 7-dagars matdagbok jämfört med kostanamnes (63% mot 32%). Det beräknade energibehovet från stegräknare och från fem av sex olika RMR ekvationer låg inom en rimlig marginal (± 10%) jämfört med den uppmätta energiförbrukningen med DLW. Beräkning av energibehov baserat på tillgänglig data om energiförbrukning mätt med DLW varierade utifrån kroppsvikt och fettfrimassa hos patienter med KOL. Kvinnor hade en lägre viloenergiförbrukning och energiförbrukning per kg kroppsvikt och dag, och högre daglig viloenergiförbrukning och energiförbrukning per kg fettfrimassa och dag jämfört med män. I den populationsbaserade studien hade personer med KOL signifikant lägre BMI och högre prevalens av undervikt än personer utan KOL. Det fanns ett oberoende samband mellan KOL och lågt BMI. Färre personer med KOL var överviktiga än personer som inte hade KOL. Kvinnor med KOL hade både lägre BMI och högre andel med undervikt än män med KOL. Slutsats SenseWear Armband med programvaran 5.1 visar sig kunna beräkna den totala energiförbrukningen på ett tillförlitligt sätt hos kvinnor med KOL. Energiintaget beräknat utifrån kostanamnes och 7-dagars matdagbok underskattades. Energibehovet kan beräknas med en rimlig precision med hjälp av stegräknare och viloenergiförbrukningsformler hos dessa kvinnor. De sammanställda data om energiförbrukning mätt med DLW kan användas för att beräkna energibehov per kg- kroppsvikt och fettfri massa hos patienter med KOL i kliniskt syfte. I det populationsbaserade materialet från OLIN-studien noterades ett lägre BMI och högre prevalens av undervikt hos personer med KOL, och detsamma resultat förekom hos kvinnor med KOL jämfört med män med KOL.