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Background:

Lung function and its trajectory throughout the life-course - starting from lung growth and maturation, followed by the attainment of peak capacity, and subsequent decline - are influenced by different interrelated factors, including smoking, overweight, obesity, traffic exposure in childhood, and asthma, with the latter being one of the most common chronic diseases in the world. Both lung function impairment and asthma carry a significant public health burden due to increased risk of morbidity, mortality, and lower quality of life. Although characterized by chronic airway inflammation and variable airflow limitation, asthma is a heterogeneous disease encompassing diverse clinical presentations and symptoms, including wheezing, difficulty breathing, and coughing. Understanding how these factors impact lung function is critical for identifying high-risk individuals in order to improve asthma outcomes and survival.

Aims:

The overall aim of this thesis is to investigate how specific respiratory symptoms and changes in body mass index (BMI) during adulthood, as well as traffic exposure in childhood, are associated with lung function and asthma. A further aim is to evaluate the association between different spirometry patterns and mortality among adults with asthma.

Methods:

This thesis is based on longitudinal data from the Obstructive Lung Disease in Northern Sweden (OLIN) research program, which used two separate population-based cohorts: the OLIN adult asthma cohort, examined at study entry (1986-2001) and at one follow-up (2012-2014), and the OLIN pediatric cohort II, recruited in 2006 at age 8 and followed up in 2016-2017 at age 19. Four prospective studies were conducted:

1. Respiratory symptoms: An analysis of 977 adults with asthma, who were followed for an average of 18 years to determine the association between the number and type of respiratory symptoms at study entry (recurrent wheeze, dyspnea, longstanding cough and productive cough) and lung function at follow-up in terms of the forced expiratory volume in one second (FEV₁) and also the annual decline in FEV₁, adjusting for other potentially associated factors by linear regression.

2. Body mass index (BMI): A study of 945 adults with asthma that investigated the impact of annual BMI change on the annual decline in FEV1, forced vital capacity (FVC) and FEV₁/FVC separately in those with normal weight (BMI 18.5–24.9) and those with overweight/obesity (BMI ≥25) at study entry. Regression models were used to adjust for sex, age, smoking, inhaled corticosteroids (ICS) use and occupational exposure to gases, dust or fumes.

3. Spirometry patterns: A mortality study of 2028 adults with asthma, where spirometry patterns at study entry were classified as normal, preserved ratio impaired spirometry (PRISm) and obstruction. Mortality data until the 31^st of December 2020 (n=720 deceased) were linked from a national register and grouped by cause: respiratory, cardiovascular, cancer and other. Cox and Fine-Gray regression models were used to estimate hazard ratios (HRs) for spirometry patterns in relation to all-cause and cause-specific mortality, adjusted for age, sex, ICS use, education level, smoking habits and BMI.

4. Traffic exposure: A 10-year follow-up of a pediatric general population cohort (n=1056), that examined the impact of childhood exposure to vehicle traffic, in an area with low traffic-flows, on lung function in young adulthood in terms of FEV₁, FVC and FEV₁/FVC. Different exposure thresholds were defined based on residence proximity (within a 200 m radius of the home address) to a road with the highest daily count of heavy vehicles (≥250 and ≥500) or any type of vehicle (≥4000 and ≥8000). The association between vehicle traffic exposure and lung function was analyzed by linear regression adjusting for potential confounders.

Results:

Respiratory symptoms associated with lung function - specifically, recurrent wheeze and a high number of concurrent symptoms - were strongly associated with lower lung function, particularly in women. Regarding weight, BMI change was significantly associated with lung function decline. This association was more pronounced in those who were already overweight or obese at study entry compared to those with a normal BMI. The mortality study showed that, in addition to smoking and obesity, both PRISm and obstruction patterns increased all-cause and respiratory mortality risks. Environmentally, even in areas with relatively low traffic flow, childhood exposure to ≥250 heavy vehicles/day and ≥8000 vehicles/day were associated with slight but significantly lower lung function in young adulthood, suggesting that there may be no "safe" threshold for traffic exposure in relation to lung function development.

Conclusions:

Early-life traffic exposure in childhood was found to be associated with slightly lower lung function in young adulthood. Among adults with asthma, recurrent wheeze was the respiratory symptom that was most strongly associated with low lung function. BMI increase was also associated with lung function decline, especially among those who were already overweight or obese. Regarding spirometry patterns, both PRISm and obstruction were associated with increased risk of all-cause and respiratory mortality. These findings highlight that symptom control and weight management among adults with asthma, as well as public health policies considering even low-level traffic exposure, are essential for preserving lung function and reducing mortality.

Background: Exposure to high levels of vehicle traffic during childhood seems to have a negative effect on lung function. Less is known about the effects of exposure to relatively low levels during childhood. We aimed to study how exposure to vehicle traffic in childhood is associated with lung function and asthma in young adulthood in a 10-year follow-up of a population-based cohort in a municipality with relatively low levels of vehicle traffic.

Methods: The Obstructive Lung Disease in Northern Sweden (OLIN) pediatric cohort II was recruited in 2006 at age 8 years. Exposure to vehicle traffic at baseline was studied in relation to lung function at follow-up at age 19 years (n = 1056 participants). Lung function measures included FEV1, FVC and FEV1/FVC. Different exposure thresholds were defined based on proximity (within a 200 m radius from the home address) to a road with a minimum daily count of heavy vehicles (≥ 250 and ≥ 500) or any type of vehicle (≥ 4000 and ≥ 8000). The association between exposure to vehicle traffic at baseline and lung function at follow-up was analyzed by linear regression adjusting for potential confounders.

Results: In general, those above the exposure thresholds had lower lung function than those below, but not significantly so in all comparisons. Those exposed to ≥ 250 heavy vehicles/day had lower mean FEV1 z-score at follow-up (-0.38) compared with those exposed to < 250 heavy vehicles/day (-0.21), p = 0.033, and this association remained after adjustment for confounders (p = 0.036). Also, those exposed to ≥ 8000 vehicles/day had lower mean FVC z-score (-0.19) than those exposed to < 8000 vehicles/day (-0.02), p = 0.047, with p = 0.032 after adjustment.

Conclusions: Exposure to vehicle traffic in childhood, in a relatively low traffic-flow environment, may be associated with a slightly lower lung function in young adulthood.

Background: With increasing prevalence of overweight and obesity, it is important to study how body mass index (BMI) change may affect lung function among subjects with asthma. There are few prospective studies on this topic, especially with separate analyses of those with normal and high BMI. The aim of the present study was to prospectively study the association between annual BMI change and annual lung function decline, separately among those with normal initial BMI and overweight/obesity, in an adult asthma cohort.

Methods: A population-based adult asthma cohort was examined at study entry between 1986 and 2001 and at follow-up between 2012 and 2014 (n=945). Annual BMI change was analysed in association with annual decline in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1 /FVC separately in those with normal weight (BMI 18.5–24.9) and overweight/obese subjects (BMI ⩾25) at study entry. Regression models were used to adjust for sex, age, smoking, inhaled corticosteroids use and occupational exposure to gas, dust or fumes.

Results: Overweight/obese subjects had lower FEV1 and FVC but slower annual FEV1 and FVC decline compared to those with normal weight. After adjustment through regression modelling, the association between BMI change with FEV1 and FVC decline remained significant for both BMI groups, but with stronger associations among the overweight/obese (FEV1 B[Overweight/obese] =−25 mL versus B[normal weight] = −15 mL). However, when including only those with BMI increase during follow-up, the associations remained significant among those with overweight/obesity, but not in the normal-weight group. No associations were seen for FEV1 /FVC.

Conclusions: BMI increase is associated with faster FEV1 and FVC decline among overweight and obese adults with asthma in comparison with their normal-weight counterparts.

Background: Asthma is a common disease and a major public health concern. Respiratory symptoms are related to its prognosis, which in turn associates with lung function. Still this association on a long-term basis is not entirely understood.

Aim: To study the association of the type and number of respiratory symptoms with FEV 1 and FEV 1 decline in women and men with asthma.

Method: A population-based cohort of adults with asthma was examined at study entry between 1986 and 2001 and at follow-up between 2012 and 2014, and n=977 had valid measurements of FEV 1 on both occasions. Data regarding respiratory symptoms at study entry (recurrent wheeze, dyspnoea, longstanding cough and productive cough) were analysed in relation to FEV 1 and annual decline in FEV 1, both unadjusted and adjusted for other potentially associated factors by linear regression.

Results: For both sexes recurrent wheeze and dyspnoea were associated with lower FEV 1 at study entry and follow-up, while productive cough was associated with lower FEV 1 only at follow-up. No associations were found between the type of symptoms and annual decline in FEV 1. In adjusted analyses, the association between recurrent wheeze and lower FEV 1 both at study entry and follow-up remained significant among women. Also, the association between a higher number of symptoms with lower FEV 1 both at study entry and follow-up were present for both sexes and remained after adjustment.

Conclusions: Particularly recurrent wheeze and a higher number of respiratory symptoms may predict lower lung function also in the long run among women and men with asthma.