Many respiratory patients misuse their inhaler. Although training improves their inhaler technique, patients do forget the correct inhaler use with time. In the current work, three clinical studies investigated novel tools designed with feedback mechanisms to ensure patients use the correct inhalation method when using their inhaler. Research Ethics Committee approval was obtained and all the participants signed an informed consent form. In the first study, the recruited asthmatic children (n=17) and adults (n=39) had their metered dose inhaler (MDI) technique assessed. Those who attained the recommended inhalation flow rate (IFR) of < 90 l/min through their MDI formed the control group. Whilst those who had a poor MDI technique with an IFR ≥ 90 l/min were randomized into either the verbal counselling (VC) group; or the 2ToneTrainer (2TT) group that, in addition to the verbal training, received the 2ToneTrainer MDI technique training device equipped with an audible feedback mechanism of correct inhalation flow. All the participants were assessed on two occasions (6 weeks apart) for their inhalation flow rate, asthma control and quality of life. The study showed that the 2ToneTrainer tool was as efficient as verbal training in improving and maintaining the asthmatic patients' MDI technique, particularly using the recommended slow inhalation flow through the MDI. Although statistically insignificant, potential improvement in quality of life was demonstrated. The 2ToneTrainer tool has the advantage of being available to the patients all the time to use when they are in doubt of their MDI technique. In the second research study, the inhalation profiles of asthmatic children (n=58) and adults (n=63), and of COPD patients (n=63) were obtained when they inhaled through the novel Spiromax dry powder inhaler (DPI) which was connected to an electronic pressure change recorder. From these inspiratory profiles; the peak inhalation flow, inhalation volume and inhalation acceleration rate were determined. The variability (23%-58%) found in these inhalation profile parameters among various patient groups would be expected in all DPIs. The effect of the inhalation acceleration rates and volumes on dose emission characteristics from DPIs should be investigated. Attention, though, should be paid to the patients' realistic inhalation profile parameters, rather than the recommended Pharmacopoeial optimal inhalation standard condition, when evaluating the in-vitro performance of DPIs. Finally, in preschool asthmatic children, the routine use of the current AeroChamber Plus spacer (n=9) was compared with that of a novel version; the AeroChamber Plus with Flow-Vu spacer (n=10) over a 12-week period. The Flow-Vu spacer has a visual feedback indicator confirming inhalation and tight mask-face seal. The study showed that the new AeroChamber Plus with Flow-Vu spacer provided the same asthma control as the AeroChamber Plus in preschool children and maintained the same asthma-related quality of life of their parents. However, the parents preferred the new Flow-Vu spacer because its visual feedback indicator of inhalation reassured them that their asthmatic children did take their inhaled medication sufficiently.

Background: Lung cancer causes more deaths than any other cancer. Smoking causes roughly 90% of lung cancer cases. Concurrent chemoradiation therapy is the standard of care for stage IIIb patients with performance status (PS) 0-1. A less toxic approach is warranted for less fit patients. To optimize care, the understanding of common clinical variables such as haematological responses to inflammation could be much improved. Adherence to guidelines for proper clinical work-up is vital to ensure patients’ optimal care, especially for predictive assays. Screening of high-risk patients is now being implemented internationally. Chronic pulmonary obstructive disease (COPD) patients, a group at high risk to develop lung cancer, could be of interest for screening. Methods: Patient cohorts collected nationally and regionally by manual search in patient records or automated search in electronic patient records and national registries were analysed in relation to overall survival, comorbidities, medication, treatment, smoking status, biomarkers and adherence to guidelines. Standard statistics were applied to adjust for confounding factors. Results: Induction chemotherapy results in longer overall survival than radiotherapy alone (15.6 and 11.6 months respectively). The overall survival for patients with combined anaemia, leucocytosis and thrombocytosis at diagnosis is half of what could be anticipated if blood samples are normal (8.0 and 16.0 months respectively). Fifty percent of patients were overlooked in the routine work-up with EGFR analysis. Less than 40% of the patients received EGFR-tyrosine kinase inhibitors in first-line therapy. The frequency of EGFR mutation was 9.9%. COPD patients with asthma and medicating with inhaled corticosteroids, specific serotonin reuptake inhibitors (SSRI) or beta-blockers have a significantly decreased risk of lung cancer. Conclusions: Patients unfit to receive chemoradiation therapy should be considered for induction chemotherapy sequentially to radiotherapy. A patient that presents with pathological blood samples is likely to have poor prognosis and diagnostic work-up should be thorough to optimize outcome. Inadequate adherence to the national guidelines regarding treatment and EGFR analysis was shown. COPD patients medicating with ICS, beta-blockers or SSRI and with a concurrent asthma diagnosis have a decreased risk of lung cancer.

Since the completion of the sequencing of the human genome at the turn of the century, genomics has revolutionized the study of biology and medicine by providing high-throughput and quantitative methods for measuring molecular activities. Microarray and next generation sequencing emerged as important inflection points where the rate of data generation skyrocketed. The high dimensionality nature and the rapid growth in the volume of data precipitated a unique computational challenge in massive data analysis and interpretation. Noise and signal structure in the data varies significantly across types of data and technologies; thus, the context of the data generation process itself plays an important role in detecting key and oftentimes subtle signals. In this dissertation, we discuss four areas where contextualizing the data aids discoveries of disease-causing variants, complex relationships in the human microecology, interplay between gene and environment, and genetic regulation of gene expression. These studies, each in its own unique way, have helped made possible discoveries and expanded the horizon of our understanding of the human body, in health and disease.

Minst 500 000 av Sveriges befolkning har kroniskt obstruktiv lungsjukdom (KOL) och ungefär 250 000 har hjärtsvikt. De två patientgrupperna hade många likartade symtom och en sjuksköterskeledd gemensam primärvårdsmottagning för dessa patienter kunde innebära många vinster. Ett av distriktssköterskans kompetensområde var att ha stödjande samtal om hur den enskilde patienten hanterade sin sjukdom. Syftet med uppsatsen var att jämföra copingförmåga och copingstrategier mellan patienter med KOL och patienter med hjärtsvikt, samt att undersöka eventuella skillnader av grad av ångest, depression, påverkan på funktion av fatigue och andfåddhet utifrån copingförmåga och användande av olika copingstrategier.  Metoden var en beskrivande och jämförande tvärsnittsstudie. Patienter med KOL respektive hjärtsvikt från primärvården i tre landsting ingick i studien och de fick svara på en hemskickad enkät. De instrument som användes i denna studie var flera, bland annat Orientation to Life Questionnaire och Ways of Coping Questionnarie. Resultat: Patienter med hög KASAM skattade de olika symtomen lägre och patienter med låg KASAM skattade de olika symtomen högre. Patienter med KOL använde sig i högre grad av olika copingstrategier än vad patienter med hjärtsvikt gjorde.  Patienter med hög grad av de olika copingstrategierna skattade de olika symptomen högre än de med låg grad av de olika copingstrategierna, med vissa undantag. Konklusion: Resultaten är intressanta och bör tas i beaktande i mötet med dessa patienter i gemensamma primärvårdsmottagningar genom råd och stöd för att minska att symtomen från KOL respektive hjärtsvikt har en negativ inverkan på deras liv. / At least 500 000 of the Swedish population have chronic obstructive pulmonary disease (COPD) and about 250 000 have heart failure. The two patient groups had many similar symptoms and a joint nurse-led primary care clinic for these patients could have many benefits. One of the district nurse's competences is supportive conversations with the individual patient about how they cope with their situation. The aim of this study was to compare coping ability and coping strategies among patients with COPD and patients with heart failure, and to investigate possible differences of degree of anxiety, depression, impact on the function of fatigue and breathlessness based on coping ability and the use of coping strategies. The method used was quantitative and comparative cross-sectional. Patients with COPD and patients with heart failure from three county primary care clinics were included in the study and they were asked to answer a questionnaire sent to their homes. The instruments used in this study were several, including Orientation to Life Questionnaire and the Ways of Coping Questionnaire. Results degree of SOC affected patients' estimation of the different symptoms. The conclusion was also that patients with COPD used in higher levels of different coping strategies than patients with heart failure did and the higher the degree of the different coping strategies, the higher the various symptoms were estimated, with some exceptions. Conclusion, the results are interesting and should be considered in the care of these patients in joint primary care clinics through advice and support to reduce the negative impact that COPD and heart failure have on their lives.

Neutrofilai ir makrofagai – vienos svarbiausių uždegiminiame procese dalyvaujančių ląstelių. Lėtinės obstrukcinės plaučių ligos (LOPL) metu aktyvintos šios ląstelės sintetina biologiškai aktyvias medžiagas, skatinančias intensyvesnį sisteminį ir kvėpavimo takuose vykstantį uždegimą. Iki šiol nėra aiškūs neutrofilų ir makrofagų sintetinamų žymenų (citokinų, proteinazių) ypatumai sergant LOPL ir atsižvelgiant į rūkymo įprotį. Nėra žinoma, kaip kraujo neutrofilų funkcines savybes tiesiogiai įtakoja pats sergančiųjų LOPL kvėpavimo takų sekretas. Šio tyrimo tikslas buvo įvertinti neutrofilų ir makrofagų funkcinių savybių ypatumus sergant lėtine obstrukcine plaučių liga ir galimus jų skirtumus priklausomai nuo rūkymo įpročio. Ištirti sergančių LOPL rūkančiųjų ir neberūkančiųjų matrikso metaloproteinazės-12 raiškos kvėpavimo takų sekreto makrofaguose ypatumai. Įvertintos sergančiųjų LOPL biologiniais ir cheminiais veiksniais aktyvintų kraujo neutrofilų funkcinės savybės (chemotaksis, fagocitozė, reaktyviųjų deguonies formų susidarymas), analizuotas potencialus moduliacinis kvėpavimo takų sekreto poveikis šioms funkcinėms savybėms. Nustatyta, jog sergančiųjų lėtine obstrukcine plaučių liga neutrofilai ir makrofagai buvo labiau aktyvūs nei sveikų asmenų ląstelės; rūkymo įprotis įtakojo kai kurias uždegimines neutrofilų ir makrofagų savybes kvėpavimo takų sekrete ir kraujyje. / Neutrophils and macrophages play an important role in inflammatory process. Activated during chronic obstructive pulmonary disease (COPD), these cells synthesize a variety of biologically active compounds, which may further amplify both systemic and local airway inflammation. The features of biologically active compounds (cytokines, proteinases) released by neutrophils and macrophages during COPD and according to smoking status are unknown. Still, a direct influence of airway mucous from COPD patients on functional neutrophil features is unknown. The aim of this study was to evaluate the functional features of neutrophils and macrophages during chronic obstructive pulmonary disease and possible differences according to smoking status. An expression of matrix metalloproteinase-12 in airway mucous of COPD smokers and ex-smokers was evaluated. The functional features (chemotaxis, phagocytosis, production of reactive oxygen species) of biologically and chemically activated blood neutrophils and a modulator effect of airway mucous were also analysed. The neutrophils and macrophages of patients with chronic obstructive pulmonary disease were more activated than the cells of healthy individuals; smoking status has influenced some inflammatory features of neutrophils and macrophages in airway mucous and blood.

No description available.

It has been established in New Zealand and internationally that morbidity and mortality tends to rise during colder winter months, with a typical 10-20% excess compared to the rest of the year. This study sought to investigate the spatial, temporal, climatic and demographic patterns and interactions of excess winter morbidity (EWMb) among the elderly in New Zealand. This was achieved through analysis of acute hospital admissions in New Zealand between 1996 and 2013 for all patients over the age of 60 with an element of circulatory or respiratory disease (N=1,704,317) including a primary diagnosis of circulatory (N=166,938) or respiratory (N=62,495) disease. A quantitative approach included ordinary least squares and negative binomial regression, graphical analysis and age standardisation processes. Admission rates and durations were regressed against a set of 16 cold spell indicators at a national and regional scale, finding significant spatial variation in the magnitude of EWMb. EWMb was ubiquitous across New Zealand despite climatic variation between regions, with an average winter excess of 15%, and an excess of 51% for chronic obstructive pulmonary disease (COPD). Statistically significant relationships were found between hospital admission durations and cold spells up to 28 days prior; however the magnitude would not be expected to have a significant impact on hospital resources. Nonetheless, there is potential for preventative public health strategies to mitigate less severe morbidity associated with cold spells. Patients over the age of 80 were particularly vulnerable to EWMb; however socioeconomic deprivation and ethnicity did not affect vulnerability. Patients residing in areas of high socioeconomic deprivation or identifying with Maori or Pacific Island ethnicity experienced significantly shorter admissions than other groups, and this warrants further investigation. Further investigation into winter COPD exacerbations and non-climatic factors associated with the EWMb are recommended. A comprehensive understanding of EWMb will enable preventative measures that can improve quality of life, particularly for the elderly population.

Abstract Introduction: Previous research showed that comorbidities that are common in patients with Chronic Obstructive Pulmonary Disease (COPD) are anxiety and depression. Furthermore, stress can be associated with more depressive symptoms. Patients suffering from depression along with an additional medical condition, tend to have more severe symptoms in both depression and their medical illness.   Aim: The aim of this study was to investigate depression, anxiety, and stress among COPD patients, and also to examine if there was a difference in levels of depression, anxiety and stress between genders, and between COPD patients and patients with COPD together with comorbid chronic condition.   Method: This study had a descriptive and cross-sectional design with a quantitative method. The data collection took place at a respiratory ward at Cho Ray Hospital in Ho Chi Minh City, Vietnam. Sixty two COPD patients, both men and women, participated voluntarily by answering a questionnaire. Virginia Henderson´s nursing theory was used as a theoretical framework. Data analysis was conducted through using the statistical program SPSS.   Result: More than half of the COPD patients (88.8%) presented symptoms of depression, 93.5% presented symptoms of anxiety, and 54.8% presented symptoms of stress. There was a statistical significance between genders among COPD patients in anxiety, where all female participants (100%) showed extremely severe levels of anxiety. In levels of extreme severity, both patients with only COPD diagnosis and patients with COPD and comorbid chronic condition presented symptoms in both depression and anxiety, but not in levels of stress.     Conclusion: COPD patients in Ho Chi Minh City presented high levels of depression and anxiety. In addition, levels of stress were present, although not as high as depression and anxiety among this patient group. More information concerning psychological distress needs to be offered by healthcare professionals to COPD patients. Further research in this field is desirable. / Sammanfattning Introduktion: Tidigare forskning visar att depression och ångest är vanligt förekommande bland patienter med Kroniskt Obstruktiv Lungsjukdom (KOL). Stress kan associeras med flera depressiva symtom. Patienter som lider av depression tillsammans med annat mediciniskt tillstånd kan ha en tendens att utveckla svårare symptom i sin depression och sitt medicinska tillstånd.   Syfte: Syftet med denna studie var att undersöka depression, ångest och stress hos patienter med KOL och om skillnader fanns mellan kön. Vidare önskades skillnader undersökas mellan patienter med enbart KOL och patienter med KOL och annat kroniskt tillstånd.     Metod: Studien är en deskriptiv tvärsnittsstudie, med kvantitativ metod. Datainsamling utfördes på en respiratorisk avdelning på Cho Ray sjukhuset i Ho Chi Minh City, Vietnam. Sextio-två KOL-patienter, både män och kvinnor, deltog frivilligt genom att besvara en enkät. Virginia Hendersons omvårdnadsteori användes i detta arbete. Dataanalysen utfördes med hjälp av SPSS programmet.   Resultat: Mer än hälften (88,8 %) av KOL-patienterna visade symtom på depression, 93,5% för ångest, samt 54,8 % visade symtom för stress. Det fanns en statistisk signifikant skillnad mellan könen avseende ångest, där alla kvinnliga deltagare (100 %) visade extremt allvarliga nivåer av ångest. Patienter med enbart KOL-diagnos och patienter med KOL tillsammans med andra kroniska tillstånd uppvisade extremt allvarliga nivåer av både depression och ångest, dock inte av stress.   Slutsats: KOL-patienter i Ho Chi Minh City, Vietnam, uppvisar höga nivåer av depression och ångest. Höga stressnivåer bland deltagare kunde ses, dock inte i lika hög utsträckning som depression och ångest i denna patientgrupp. Mer studier i detta ämne är önskvärt.

Lėtinė obstrukcinė plaučių liga (LOPL) – šiuo metu pasaulyje viena svarbiausių didelį sergamumą ir mirtingumą sąlygojančių ligų. Pacientams, kuriems pasunkėja kasdieniai LOPL simptomai pasireiškia LOPL paūmėjimas. Šio tyrimo tikslas – įvertinti nespecifinį uždegimą paūmėjus lėtinei obstruk¬cinei plaučių ligai. Nustatyti periferinio kraujo ir indukuotų skreplių ląstelių sudėties skirtumai ir įvertintos sąsajos su plaučių funkcijos rodikliais bakterinio ir nebakterinio lėtinės obstrukcinės plaučių ligos paūmėji¬mo metu. Tirtos sergančiųjų bakterinės kilmės lėtinės obstrukcinės plaučių li¬gos paūmėjimo indukuotų skreplių neutrofilų ir makrofagų funkcijos (apoptozė, fagocitozė ir reaktyvių deguonies formų susidarymas) bei palygintos su nebakteriniu paūmėjimu. Įvertinti sergančiųjų bakterinės ir nebakterinės kilmės lėtinės obs¬trukcinės plaučių ligos paūmėjimo periferinio kraujo neutrofilų ir monocitų apoptozė ir chemotaksis, bei periferinio kraujo neutrofilų fagocitozė ir reaktyvių deguonies formų susidarymas. Ištirta sergančiųjų bakterinės ir nebakterinės kilmės lėtinės obstruk¬cinės plaučių ligos paūmėjimu interleukino-8 koncentracija ir sąsajos su periferinio kraujo neutrofilų chemotaksiu bei C reaktyviojo baltymo koncentracijos periferinio kraujo serume sąsajos su plaučių funkcija ir rūkymo intensyvumu. / Chronic obstructive pulmonary disease (COPD) – a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. An acute exacerbation of COPD (AECOPD) is an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication. The aim of this study was to evaluate the non-specific inflammation during acute exacerbation of COPD to investigate change of cellular activity (apoptosis, chemotaxis, phagocytosis and production of reactive oxygen species) during AECOPD depending on infection agent. Subjects with AECOPD and the same in remission were investigated. Increased count of induced sputum neutrophils and macrophages as well peripheral blood neutrophils and monocytes during bacterial and non-bacterial AECOPD was related with impaired pulmonary function and smoking history. Induced sputum neutrophils and macrophage apoptosis and phagocytosis were weaker, but production of reactive oxygen species was strongly activated during bacterial acute exacerbation of chronic obstructive pulmonary disease than non-bacterial AECOPD. This study showed differences of peripheral blood neutrophil and monocyte apoptosis, chemotaxis, as well as peripheral blood neutrophil phagocytosis and the production of reactive oxygen species... [to full text]

Preliminary evidence suggests that balance deficits constitute an important secondary impairment in individuals with chronic obstructive pulmonary disease (COPD). The main objective of this thesis was to describe balance impairment and fall risk in individuals with COPD and to examine interventions for improving balance and reducing fall risk in the context of pulmonary rehabilitation. The first study of this thesis showed that falls are common in patients with COPD and that fallers are characterized by impairments in standard clinical balance measures, such as the Berg Balance Scale and Timed Up and Go. In the second study, we found that the exercise component of conventional pulmonary rehabilitation has only modest effects on balance and fall risk in COPD, highlighting the need to examine the role of balance-specific training for these patients. The third study of this thesis identified the postural control subsystems most responsible for the observed balance deficits in COPD. Compared with age-matched controls, individuals with COPD demonstrated reductions in all balance control subsystems and slower reaction times in response to external perturbations. In this study, we also showed that deficits in balance in patients with COPD were associated with peripheral muscle weakness and reduced physical activity levels. These results informed the design of the final study of this thesis, a randomized controlled trial evaluating the addition of specific balance training to pulmonary rehabilitation for improving balance in patients with COPD. Preliminary results from this study suggest that the addition of thrice weekly balance exercises to a conventional pulmonary rehabilitation program is effective for optimizing gains in measures of functional balance and fall risk. The findings from the four studies included in this thesis support the need for incorporating balance assessment and treatment for at-risk patients with COPD, as part of their comprehensive management.