Kinder, welche nach 34 (+0) bis 36 (+6) Gestationswochen geboren werden, bezeichnet man als späte Frühgeborene. Genau wie Kinder eines jüngeren Gestationsalters sind diese von einer höheren postnatalen Morbidität und Mortalität betroffen als reif geborene Kinder. Diese Studie betrachtet die pulmonale Funktionsleistung dieser Kinder weit über die Neonatalperiode hinaus. Ehemals späte Frühgeborene wurden im Alter von 6 Jahren untersucht. Eine gleichaltrige Kontrollgruppe, bestehend aus ehemals reifen Neugeborenen, diente dem Vergleich. Vor allem Parameter der Spirometrie sowie Peak-Flow- und Atemwegswiderstandsmessungen ermöglichten dabei die Objektivierung der pulmonalen Funktion. Statistisch signifikante Unterschiede ließen sich in der mittleren FVC (forcierte Vitalkapazität) sowie dem FEV1 (forciertes exspiratorisches Volumen in einer Sekunde) feststellen, wobei Kinder der Indexgruppe jeweils im Mittel nur geringere Werte erreichten als Kinder der Kontrollgruppe. Der mittlere Atemwegswiderstand unterschied sich in Index-und Kontrollgruppe ebenso signifikant, wobei bei ehemals späten Frühgeborenen der Atemwegswiderstand im Mittel höher war als bei ehemals reifen Neugeborenen.

Genetic studies of lung disease in Cystic Fibrosis are faced with the challenge of identifying a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment. This thesis uses data from the North American Cystic Fibrosis Modifier Consortium (Canadian Consortium for CF Genetic Studies (CGS), Johns Hopkins University Twins and Siblings Study (TSS), and University of North Carolina/Case Western Reserve University Gene Modifier Study (GMS)), to calculate two novel phenotypes using age-specific CF percentile values of FEV1 (Forced Expiratory Volume in 1 second), with adjustment for CF age-specific mortality. The normalized residual, mortality adjusted (NoRMA) was designed for population based samples, while KNoRMA, using Kulich percentiles, is robust to sample ascertainment; both account for the effects of age-related disease progression and mortality attrition. NoRMA was computed for 2122 patients representing the Canadian CF population. KNoRMA was computed for these 2122 patients and also 1137 extreme phenotype patients in the GMS study and 1323 patients from multiple CF sib families in the TSS study. Phenotype was distributed in all three samples in a manner consistent with ascertainment differences, reflecting the lung disease severity of each individual in the underlying population. The new phenotype was highly correlated with the previously recommended mixed model phenotype1; 2, but computationally much easier and suited to studies with limited follow up time. As an example of its use, KNoRMA was used to test the association between locus variants in a previously published candidate gene, Transforming Growth Factor β1(TGFβ1), and lung function in CF, in an attempt to provide insight into discrepant results in the literature. A disease progression and mortality adjusted phenotype reduces the need for stratification or additional covariates, increasing statistical power and avoiding possible interpolation distortions.

Doctor of Philosophy(PhD) / Over the last 20 years both asthma and obesity have increased in prevalence. What is the link? There are data to suggest that increasing obesity is a risk for the increase in prevalence of asthma. A number of mechanisms have been postulated including the effects of reduced lung volume on bronchial reactivity and mechanical changes with lower lung volumes. Other possibilities include other obesity-induced co-morbidities including gastro-oesophageal reflux. The aim of this thesis was to evaluate the link between asthma and obesity in both adult and childhood populations and to undertake experimental studies to examine the effects of changes in lung volume on bronchial reactivity. In chapter 1, the literature is reviewed. The current literature suggests that there is a link between diagnosis of asthma, new onset of asthma, symptoms of shortness of breath and wheeze. In chapter 2, data on 1997 adults in 3 population studies were analysed and the association between body mass index (BMI) and symptoms of shortness of breath and wheeze, diagnosis of asthma, medication usage for asthma, lung function and bronchial responsiveness were studied. This study showed that obesity was a risk for recent asthma (OR 2.04; 95%CI 1.02-3.76, p=0.048), symptoms of shortness of breath and wheeze (OR 2.6; 95%CI 1.46- 4.70, p=0.001), and medication usage for asthma (OR 2.53; 95%CI 1.36-4.70, p=0.003). There was a reduction in lung volume as measured by forced vital capacity (FVC), but there was no increase in bronchial hyperresponsiveness (BHR) (OR 0.87; 95% CI 0.35-2.21, p=0.78). Thus although the symptoms of asthma are increased there were no increases in BHR, despite significantly reduced lung volumes. The increase the medication usage is unlikely to have normalised the BHR, as there were ongoing symptoms suggestive of asthma. In chapter 3, data on 5993 children in 7 population studies were analysed and the association between BMI percentile and symptoms of cough, wheeze, ix diagnosis of asthma, medication usage for asthma, atopy, lung function and bronchial responsiveness was studied. After adjusting for atopy, sex, age, smoking and family history, BMI was a significant risk factor for wheeze ever (OR=1.06; 95%CI 1.01-1.10, p=0.008) and cough (OR=1.09; 95%CI 1.05-1.14, p=0.001) but not for recent asthma (OR=1.02; 95%CI 0.98-1.07 p=0.43), or bronchial hyperresponsiveness (OR=0.97; 95%CI 0.95-1.04 p=0.77). In girls, a higher BMI was significantly associated with higher prevalence of atopy (x2 trend 7.9, p=0.005), wheeze ever (x2 trend 10.4, p=0.001), and cough (x2 trend 12.3, p<0.001). These were not significant in boys. With increasing BMI in children, there was no reduction in lung volume, no increase in airway obstruction and no increase in bronchial responsiveness. In chapter 4, the hypothesis that obesity per se is associated with bronchial responsiveness was tested. Six obese women without asthma were compared to 6 non-obese women without asthma with high dose methacholine challenges to assess the bronchial responsiveness. There was no increase in bronchial responsiveness, and no difference in the position or shape of the high dose methacholine curve despite the fact that these women had reduced lung volumes associated with their obesity. In chapter 5, the hypothesis whether reduced lung volume per se would cause a change in greater mechanical effect, ie more marked airway narrowing in both non-asthmatic and asthmatic subjects was tested. Lung volumes and methacholine challenges were undertaken in the supine and erect position on different days. As expected in normal subjects there was a small reduction in lung volume on lying down, this was associated with an increase in the measure of bronchial reactivity DRR. In contrast, in asthmatics, there was no acute fall in lung volume and there were variable changes in the index of reactivity suggesting non-homogeneity in the lung function abnormality. This suggests changes in bronchial reactivity can occur without any relationship to lung volume change. These negative results suggest that lung volume changes that may occur in obesity are unlikely contributors to the apparent increase in asthma symptoms. In chapter 6, the hypothesis that the supposed increase in asthma symptoms in the obese were due to the effects of gastro-oesophageal reflux were assessed in 147 obese subjects graded for gastro-oesophageal reflux severity using manometry and gastroscopy. This study showed that subjects with increased gastro-oesophageal reflux did not have subjective increases in asthma prevalence, obstructive sleep apnoea, or snoring however they had a clear worsening of gas transfer as measured by carbon monoxide transfer suggesting a greater level of parenchymal disease. The overall results are that there is an increase of diagnosis of asthma, increase in symptoms of asthma and medication usage for the treatment of asthma in the obese. Objectively despite reductions in lung volume, there is no increase in bronchial responsiveness in this group suggesting that these symptoms are not related to true asthma, but to alternative co-morbidities associated with obesity such as gastro-oesophageal reflux. Notably gastrooesophageal reflux was not associated with increased asthma prevalence or airway obstruction. However it was associated with reduced gas transfer suggesting parenchymal disease. This suggests that the increase in symptoms of wheeze and shortness of breath in the obese should not be attributed to asthma in the absence of variable airflow limitation that is reversible spontaneously or with treatment, or with an increase in the existing bronchial hyperresponsiveness (BHR) to a variety of stimuli.

Asthma is the most common chronic disease in children and the effects of air pollution exposure on asthma and respiratory health in children have been a growing concern over recent decades. Although a number of epidemiological studies have been carried out in this field, these have produced conflicting results. The aim of this study was to assess the effects of long term exposure to nitrogen dioxide (NO2) and particulate matter (PM10) on asthma prevalence and lung function in children. To achieve this, a novel exposure model was developed and evaluated, which allowed retrospective exposure assessment of children participating in a population based birth cohort study – the Manchester Asthma and Allergy Study (MAAS). MAAS is a prospective birth cohort study comprising 1185 children specifically designed to study asthma and allergies. Clinical follow up took place at ages 3, 5, 8 and 11 years. At each follow up parents completed questionnaires on asthma diagnosis and symptoms and children underwent skin prick tests for common allergens. Children’s specific airways resistance (sRaw, at ages 3, 5, 8, 11) and forced expiratory volume in one second (FEV1, at ages 5, 8, 11) were measured. At ages 5 and 11 years FEV1 was measured at baseline and after bronchodilator treatment. The exposure model developed during this study incorporated outdoor and indoor air pollution, spatio-temporal variation in air pollution and time-activity patterns of children. The model was based on the concept of microenvironmental exposure. It modelled personal exposure based on PM10 and NO2 concentrations in children’s home, school and journey microenvironments (MEs) and the length of time they spend in these MEs. Land use regression (LUR) models were used to model PM10 and NO2 concentrations in outdoor MEs. These LUR models were specifically developed for the Greater Manchester area. A novel method was used to develop the LUR models, which used the output from an air dispersion model as dependent variables in the regression analysis. Furthermore, a novel approach was used to obtain annual concentration of PM10 and NO2 from 1996 to 2010, which involved the recalibration of the LUR models for each year. A mass balance model and indoor to outdoor ratios were used to model concentrations in indoor MEs. The performance of the exposure model was evaluated through a personal monitoring study in schoolchildren attending a local secondary school. Children wore personal NO2 monitors for two consecutive days in four seasons. Parental questionnaires and time-activity diaries were used to obtain information for the exposure model and to model NO2 exposure for the same time period. The results showed good agreement between monitored and modelled NO2 concentrations (Normalised mean bias factor=-0.04). Multiple linear regression and generalised estimating equations (GEE) were used to assess the cross-sectional and longitudinal effect of modelled exposure on sRaw and FEV1 (as % predicted). Multiple logistic regression and GEE were used to assess the effect of modelled exposure on the prevalence of asthma and current wheeze.The longitudinal analyses showed significant associations between PM10 and NO2 exposure and % predicted FEV1 (PM10: B=-1.37, p=0.019; NO2: B=-0.83, p=0.003), but no association with sRaw (PM10: B=0.009, p=0.37; NO2: B=-0.007, p=0.16). The cross-sectional analyses showed no association between pollutant exposure during the summer or winter prior to age 11 and any of the lung function measures (p>0.05). Long term PM10 or NO2 exposure were not associated with asthma or current wheeze (p>0.05).This study developed and evaluated a novel air pollution exposure model for epidemiological research. The results of this study suggest a negative impact of long term exposure to NO2 and PM10 on growth in FEV1 during primary school age. However, no evidence of an association between long term exposure to NO2 and PM10 and childhood asthma was found.

Background: Although several reports have shown an adverse cardiovascular and metabolic risk profile associated with childhood obesity, few reports have examined the effects of childhood obesity on pulmonary function. Objective: The purpose of this study was to examine the influence of obesity on pulmonary function in Navajo and Hopi children. Methods: Subjects included 256 (110 males, 16 females) Hopi children 6-12 years of age and 557 (274 males, 283 females) Navajo children 6-12 years of age (N=813). The body mass index was used to classify subjects as normal weight, overweight, or obese on the basis of international reference values. Forced vital capacity (FVC), forced expired volume in one second (FEVl), FEV1% (FEV1 to FVC ratio; FEV1/FVC), and forced expiratory flow between 25%-75% of vital capacity (FEF25-75) were determined according to the American Thoracic Society recommendations. Results: Approximately 26% of Navajo and Hopi children were defined as overweight (26.0% of boys and 25.6% of girls) and an additional 16% (14.6% of boys and 17.7% of girls) were defined as obese. In general, the patterns showed an increase in pulmonary function between normal weight and over-weight children and a decrease in pulmonary function of obese children. Significant differences among groups existed for FEV1% and FEF25-75 in boys and FVC and FEV1 in girls. Conclusions: The results indicate the pulmonary consequences of obesity in children and provide further evidence of the adverse consequences, of pediatric obesity among Native Americans.

No description available.

Thesis (MScPhysio)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Background: Pulmonary tuberculosis (PTB) remains a major concern worldwide. Although PTB is curable, both the disease and its treatment may have considerable medical, social and psychological consequences which may result in a decreased quality of life and functioning. Characterization of the functional capabilities of PTB patients post-treatment and the impact of PTB on their quality of life may identify a need for more holistic management of PTB treatment that extends beyond microbiological cure. Methods: Firstly, an in-depth scoping review was conducted using the following key words: Pulmonary tuberculosis (MESH term) and Health related quality of life (HRQoL), Pulmonary tuberculosis (MESH term) and Spirometry and Pulmonary tuberculosis (MESH term) and Six minute walk test or 6MWT to review the current literature reporting on the HRQoL, lung function measurements and exercise capacity of a PTB population (Chapter 2). Secondly, a cross-sectional, quantitative, descriptive study was conducted. The study setting included five primary health care facilities (PHCF) in the Breede Valley sub-district of the Cape Winelands East District, Western Cape, South Africa. Adult patients diagnosed with PTB, 18 years and older and who were successfully managed through the Cape Winelands District Health Care system were considered for the study if they had least two negative sputum sample results and had completed at least five months of anti-tuberculosis treatment. Post treatment bronchodilator lung function tests, health related quality of life using the BOLD core questionnaire and six minute walk test distance (6MWD) was measured. Findings: The comprehensive broad search of the literature yielded a total of 2446 articles. A total of 2422 articles were excluded since the title; abstract or full text article did not conform to the review question or were eliminated as duplicates across databases. Twenty-seven articles divided amongst the three subsections i.e. PTB and HRQoL (n=13), PTB and Spirometry (n=9) and PTB and exercise capacity (n=6), were included in the review. In the cross-sectional study, 328 names were obtained from the TB registers of the five included PHCF of which 45 patients were included in the study (56% male; mean age, 39.88±10.20 years). The majority of patients (n= 206; 63%) were not contactable, and could not be recruited. Approximately half the total sample, (n=23; 52%) presented with normal lung function while n=11 (25%) presented with a restrictive pattern, n=9 (21%) presented with an obstructive pattern and only n=1 (2%) presented with a mixed pattern (defined as FEV1<80% predicted, FVC<80% predicted and FEV1/FVC<0.7). The mean six minute walk distance (6MWD) was 294.5m±122.7m. Respondents scored poorly on all sub-domains of the SF-12v2 except vitality. Role emotional and role physical scored lowest with mean scores of 28.1 and 35.27 respectively, while vitality scored the highest with 52.78. Stellenbosch University https://scholar.sun.ac.za 4 | P a g e Conclusion The findings of this thesis suggest that even after microbiological cure, PTB patients may suffer from a decreased quality of life, impaired lung function and a decreased exercise capacity. Specific challenges to data collection in a rural region were identified; which included patient recruitment, field testing of exercise capacity (6MWD), and the generalizabilty of standardized questionnaires in rural regions. The findings of this pilot study serves to inform the planning of a larger observational study, in the rural Cape Winelands of the Western Cape, South Africa. / AFRIKAANSE OPSOMMING: Agtergrond Pulmonêre tuberkulose (PTB) wek wêreldwyd steeds groot kommer. Hoewel dit geneeslik is, kan die siekte sowel as die behandeling daarvan beduidende mediese, maatskaplike en sielkundige gevolge hê, wat lewensgehalte en funksionering kan knou. Die tipering van PTB-pasiënte se funksionele vermoëns ná behandeling sowel as die impak van PTB op hul lewensgehalte kan dalk dui op ’n behoefte aan die meer holistiese bestuur van PTB-behandeling, wat méér as blote mikrobiologiese genesing insluit. Metodes Eerstens is ’n diepgaande bestekstudie aan die hand van die volgende trefwoorde onderneem: pulmonêre tuberkulose (MeSH-term) en gesondheidsverwante lewensgehalte (HRQoL), pulmonêre tuberkulose (MeSH-term) en spirometrie, en pulmonêre tuberkulose (MeSH-term) en die ses minute lange stapafstandtoets (6MWT). Na aanleiding daarvan is die huidige literatuur oor die HRQoL, longfunksiemetings en oefenvermoë van ’n PTB-populasie bestudeer (hoofstuk 2). Tweedens is ’n kwantitatiewe, beskrywende deursneestudie onderneem. Die studie-omgewing het bestaan uit vyf fasiliteite vir primêre gesondheidsorg in die Breedevallei-subdistrik van die streek Kaapse Wynland-Oos, Wes-Kaap, Suid-Afrika. Volwasse pasiënte van 18 jaar en ouer wat met PTB gediagnoseer is en suksesvol deur die distriksgesondheidsorgstelsel van die Kaapse Wynland-streek bestuur word, is vir die studie oorweeg indien minstens twee van die pasiënt se sputummonsters TB-negatiewe resultate opgelewer het en die persoon reeds minstens vyf maande vir tuberkulose behandel is. Studiemetings het ingesluit brongodilator-longfunksietoetse ná behandeling, gesondheidsverwante beoordelings van lewensgehalte met behulp van die BOLD-vraelys, en die aflegging van ’n ses minute lange stapafstandtoets (6MWT). Bevindinge Die omvattende breë soektog van die literatuur het 'n totaal van 2446 artikels opgelewer. 'n Totaal van 2422 artikels is uitgesluit, aangesien die titel; abstrakte of volledige teks artikel het nie voldoen aan die navorsings vraag, of is uitgeskakel as duplikate oor databasisse. Sewe en twintig artikels verdeel tussen die drie onderafdelings, naamlik PTB en HRQoL (n = 13), PTB en Spirometrie (n = 9) en PTB en oefening kapasiteit (n = 6), is ingesluit in die oorsig. In die deursneestudie is 328 name uit die TB-registers van die vyf ondersoekpersele bekom. Altesaam 45 pasiënte (56% mans; gemiddelde ouderdom 39.88±10.20 jaar) is by die studie ingesluit. Die oorgrote meerderheid pasiënte (n = 206; 63%) kon nie bereik word nie, en dus ook nie gewerf word nie. Ongeveer die helfte van die algehele steekproef (n = 23; 52%) se longfunksie was normaal; n = 11 (25%) het ’n restriktiewe patroon getoon; n = 9 (21%) ’n obstruktiewe patroon, en slegs n = 1 (2%) ’n gemengde patroon (wat omskryf word as ’n FEV1-voorspellingswaarde van <80%, ’n FVC-voorspellingswaarde van <80%, en FEV1/FVC van <0.7). Die gemiddelde afstand wat in die ses minute lange staptoets afgelê is (6MWD), was 294,5 m±122,7 m. Respondente behaal swak Stellenbosch University https://scholar.sun.ac.za 6 | P a g e op al die sub-domein van die SF-12v2 behalwe vitaliteit. Rol emosionele en rol fisiese behaal laagste met die gemiddelde tellings van 28.1 en 35,27 onderskeidelik, terwyl vitaliteit behaal die hoogste met 52,78. Gevolgtrekking Die bevindinge van hierdie tesis gee te kenne dat PTB-pasiënte selfs ná mikrobiologiese genesing dalk swakker lewensgehalte, verswakte longfunksie en ’n afname in oefenvermoë ondervind. Bepaalde uitdagings vir data-insameling in ’n landelike omgewing is uitgewys, onder meer pasiëntewerwing, veldtoetsing van oefenvermoë (6MWD) en die veralgemeenbaarheid van gestandaardiseerde vraelyste in landelike gebiede. Die bevindinge van hierdie proefstudie kan gebruik word om die beplanning van ’n groter waarnemingstudie in die landelike Kaapse Wynland-streek in die Wes-Kaap, Suid-Afrika, te rig.

INTRODUCTION: Airway inflammatory response is widely believed to be a central mechanism in the development of adverse health effects related to air pollution exposure. Increased ventilation and inspiratory flow rates due to physical activity in the presence of air pollution will increase the inhaled dose of air pollutants. However, physical activity can also affect lung function and may moderate the relationship between air pollution and lung function. The mechanisms that underpin the complex interplay between air pollution, physical activity, and lung function may be more sensitive to the inhaled dose of air pollution than to ambient air pollution exposure alone. Despite this, the majority of literature on the topic measures only the ambient concentration of air pollution. AIM: This study aims to characterize the relationship between inhaled air pollution dose, physical activity, and respiratory response markers of lung function, oxidative stress and inflammation among healthy adolescents. Respiratory response measures include exhaled nitric oxide (eNO), percent oxidized exhaled breath condensate glutathione (%GSSG), percent oxidized exhaled breath condensate cysteine (%CYSS), the percentage of total oxidized compounds (%Oxidized), and changes in pulmonary function, namely, forced vital capacity (FVC), forced expiratory volume (FEV1), and forced expiratory flow (FEF25-75). Air pollution measures include cumulative inhaled doses of fine particulate matter (PM2.5), ozone (O3), black carbon (BC), and particle number total (PNT). METHODS: Using a non-probability sample of high school athletes, outcomes were measured prior to and after participation in extracurricular sports practice. The inhaled dose of air pollutants during the sports practice was estimated for each participant using a novel method developed by Dr. Roby Greenwald. This observational study estimates the association between air pollution dose and outcome measures using general linear mixed models with an unstructured covariance structure and a random intercept for subject to account for repeated measures within subjects. All data analysis was completed using SAS. RESULTS: A one IQR (i.e. 345.64 µg) increase in O3 inhaled dose is associated with a 29.16% average decrease from baseline in %Oxidized. A one IQR (i.e. 2.368E+10 particle) increase in PNT inhaled dose is associated with an average decrease in FEF25-75 of 0.168 L/second from baseline. The relationship between PNT inhaled dose and eNO is moderated by activity level, with increasing activity levels attenuating the relationship. Similarly, the relationship between O3 inhaled dose and %CYSS is attenuated by activity level, with increasing activity levels corresponding to smaller changes from baseline for a constant O3 inhaled dose. DISCUSSION: Someone who inhales a high cumulative dose despite a low activity level is likely breathing in a higher concentration of air pollution in a shorter period of time than a person who receives the same dose with a high activity level. The moderating effects of activity level suggest that peaks of high concentration doses of air pollution may overwhelm cells’ endogenous redox balance resulting in increased airway inflammation. Further research that examines the relationships between dose peaks over time and inflammation could help to determine whether a high concentration dose over a short period of time has a different effect than a lower concentration dose over a longer period of time.

Background A significant proportion of children are exposed to environmental tobacco smoke (ETS) throughout the world. This is mainly because of exposure to parental smoking. It is unknown to what extent the negative effects of ETS on respiratory symptoms track from childhood into adulthood. Methods TESAOD (Tucson Epidemiologic Study of Airway Obstructive Disease) is a large population-based prospective study that was initiated in 1972. Participants were followed prospectively with questionnaires and pulmonary function tests (PFTs) completed about every two years in 12 follow-up surveys up to 1996. Skin prick tests and blood samples for IgE measurements were collected at surveys 1, 6, and 11. We identified subjects who entered the study as children (<15 years old) and were followed to adulthood (>18 years) during the study follow-up. Based on questionnaire data, active asthma, wheeze, cough, and chronic cough (cough for three consecutive months) were coded as never (never reported in childhood or adulthood), incident (never reported in childhood, but ≥ one positive report in adulthood), remittent (≥ one positive report in childhood, but not in adulthood), and persistent (≥ one positive report both in childhood and adulthood). PFTs measurements included forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow at 25-75%. Parent information on smoking status was collected simultaneously at child visits. ETS exposure status was assessed as “ever” or “never” between birth and 15 years. Results Information on parental ETS exposure in childhood and outcomes in adulthood was available for 444 non-Hispanic white participants (51.4% male) with mean age at initial survey of 7.7 years. Total mean follow-up time was 19.0 years (8.8 years in adulthood). Between birth and 15 years, 53.4% of children were exposed to ETS. After adjusting for sex, age at enrollment, years of follow-up, and personal smoking status (assessed at age 15 and above), combined parental ETS exposure in childhood was significantly associated with persistent wheeze (RR(adj) 1.9, p=0.026), persistent cough (RR(adj) 5.9, p<0.001), and persistent (RR(adj) 3.7, p=0.030) and incident chronic cough (RR(adj) 2.3, p=0.040). Paternal ETS exposure in childhood was associated with persistent wheeze (RR(adj) 2.3, p=0.002), persistent cough (RR(adj) 3.9, p<0.001), persistent (RR(adj) 4.8, p=0.004) and incident chronic cough (RR(adj) 2.2, p=0.031), and persistent asthma (RR(adj) 2.3, p=0.016). Maternal ETS exposure was associated with persistent (RR(adj) 1.9, p=0.029) and incident cough (RR(adj) 2.5, p=0.006). Maternal ETS exposure was associated with an increased percent predicted FVC in adulthood (coefficient, 3.75; p=0.019). No other effects on lung function were seen. There were no effects of ETS exposure on total serum IgE or allergic sensitization. ETS exposure was associated with respiratory symptoms in adulthood among both never and current smokers. Conclusions ETS exposure in childhood has long term health effects on lung function and respiratory symptoms. These effects do not appear to be IgE-mediated. ETS exposure, especially paternal ETS exposure, seems to influence the persistence of respiratory symptoms from childhood to adulthood and to affect women more than men. These effects are independent of personal smoking and also seen in never smokers. Both smoking mothers and fathers should be targeted when attempting to reduce ETS exposure among children.

Background: Exercise capacity (EC) is widely recognized as a strong and independent predictor of mortality and disease progression in various diseases, including cardiovascular and pulmonary diseases. Furthermore, it is generally accepted that exercise capacity in healthy individuals and in patients suffering from cardiovascular diseases is mainly limited by the maximum cardiac output. Objectives: This thesis investigated the impact of different lung function indices on EC in healthy individuals, patients with cardiovascular disease (e.g., pulmonary hypertension (PH)) and patients with pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD)). Methods: The present thesis is based on cross-sectional and longitudinal analyses of patients suffering from COPD, attending pulmonary rehabilitation at Uppsala University Hospital (studies I and II), and healthy men enrolled in the “Oslo ischemia study” (study IV). Study III is a cross-sectional study of patients suffering from PH attending the San Giovanni Battista University Hospital in Turin. EC was assessed using a bicycle ergometer in studies I and IV, with 12-minute walk tests (12MWT) in study II and with 6-minute walk tests (6MWT) in study III. Extensive pulmonary function tests, including diffusing capacity of the lung (DLCO), were performed in studies I-III and dynamic spirometry was used to assess lung function in study IV. Results: DLCO is more closely linked to decreased levels of EC than airway obstruction in COPD patients. Furthermore, the decline in 12MWT over a 5-year period was mainly explained by deterioration in DLCO in COPD patients. Spirometric parameters indicating airway obstruction significantly related to EC and exercise-induced desaturation in PH patients. A significant, but weak association between lung function parameters and EC was found in healthy subjects and this association is strengthened with increasing age. Conclusion: DLCO is the strongest predictor of low EC and EC decline in COPD. In PH, airway obstruction is strongly related to reduced 6MWT. Therefore, extensive analysis of lung function, including measurements of diffusing capacity, along with standard assessment of airway obstruction, gives a more comprehensive assessment of the functional exercise capacity in patients suffering from pulmonary hypertension or COPD. Lung function is also significantly linked to EC even in healthy subjects, lacking evident cardiopulmonary diseases.