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Background: Respiratory symptoms are common in the general adult population. Increased burden of respiratory symptoms may increase the risk of mortality. We assessed the association between respiratory symptom clusters and mortality.

Methods: Participants were derived from two population-based Swedish adult cohorts (N = 63,060). Cluster analysis was performed with Locality Sensitive Hashing (LSH)-k-prototypes in subjects with ≥ 1 self-reported respiratory symptom. Linked mortality register data (up to 21 years of follow-up, > 600,000 person-years) were used. Associations between clusters and all-cause/cause-specific mortality were assessed using asymptomatic subjects as reference.

Results: Over 60% reported ≥ 1 respiratory symptom and ~ 30% reported ≥ 5 respiratory symptoms. Five clusters were identified, partly overlapping with established respiratory disease phenotypes but many individuals were undiagnosed: (1) "low-symptomatic" (30.3%); (2) "allergic nasal symptoms" (10.7%); (3) "allergic nasal symptoms, wheezing, and dyspnea attacks" (4.7%); (4) "wheezing and dyspnea attacks" (6.6%); (5) "recurrent productive cough and wheezing" (4.1%). All but Cluster 2 were associated with all-cause mortality, highest risk for Cluster 3 (hazard ratio 1.4, 95% confidence interval 1.13–1.73) and Cluster 5 (1.4, 1.22–1.61). Comparable associations were seen for cardiovascular mortality. For respiratory mortality, Cluster 4 (2.02, 1.18–3.46) and Cluster 5 (1.89, 1.1–3.25) were most strongly associated.

Conclusions: Respiratory symptoms are common in the general adult population, with identifiable clusters. These clusters have clinical relevancy as they are differentially associated with mortality and relatively weakly correlated with diagnosed respiratory disease.

Background: Longitudinal studies on allergic rhinitis (AR) incidence and remission from childhood to adulthood are limited. This study aimed to estimate AR incidence and remission from age 8 to 19 years and to identify related risk factors.

Methods: In 2006, all children in grades 1 and 2 (median age 8 years) in three municipalities in Northern Sweden were invited to participate in a questionnaire survey. The children in two of the municipalities underwent a skin prick test (SPT) for airborne allergens. The protocol was repeated at age 19 years. In total, 2250 participants (91% participation rate) completed the questionnaire, and 1338 underwent SPTs at 8 and 19 years of age.

Results: From age 8 to 19 years, the cumulative incidence of AR was 33.6%, significantly higher among girls than boys (37.4% vs. 29.8%, p <.001). Factors that independently increased the risk of developing AR were sensitisation by age 8 (adjusted odds ratio [aOR] 3.75, 95% confidence interval [CI] 2.68–5.23), sensitisation between 8 and 19 years (aOR 2.57, 95% CI 1.82–3.63), and female sex (aOR 1.71, 95% CI 1.30–2.26). The remission rate was 40.0%, with boys experiencing significantly higher remission than girls (45.4% vs. 32.2%, p =.015). The probability of remission was decreased by sensitisation before (aOR 0.26, 95% CI 0.13–0.53) and after age 8 years (aOR 0.20, 95% CI 0.05–0.77).

Conclusion: This study found a high incidence of AR between age 8 and 19 years, especially among girls, while boys had a higher remission rate. Sensitisation increased the risk of developing AR and decreased the remission rate.

Background: Individuals with a restrictive spirometric pattern have a high burden of cardiovascular and metabolic morbidity.

Objective: To assess prevalence of elevated cardiac biomarkers among individuals with a restrictive spirometric pattern compared to those with a normal lung function and to evaluate the association between cardiac biomarkers and mortality.

Methods: In 2002–04, individuals with airway obstruction were identified from population-based cohorts, together with age- and sex-matched non-obstructive referents. The analysis population consisted of the non-obstructive referents stratified according to whether they had a restrictive spirometric pattern or normal lung function in whom cardiac biomarkers were measured. Deaths were recorded until 31 December 2010.

Results: Participants with a restrictive spirometric pattern were older and more likely to be obese with a higher burden of cardiovascular risk factors than those with normal function. Elevated cardiac troponin but not natriuretic peptide levels were more common in those with a restrictive spirometric pattern independent of age, sex, BMI, or risk factors (adjusted OR 1.8, 95% CI 1.29–2.74). At 5 years, death occurred more frequently in participants with restrictive spirometric pattern compared to those with normal function (15.7% [31/197] versus 7.6% [57/751]), with highest mortality rate in those with restriction and elevated cardiac troponin (28.7% [27/94]). Cardiac troponin was independently associated with death among those with a restrictive spirometric pattern (HR 4.91, 95% CI 1.58–15.26) but not in those with normal lung function.

Conclusion: Cardiac troponin was elevated more often in people with a restrictive spirometric pattern in whom it was a strong independent predictor of death.

Introduction: Computational sciences have significantly contributed to characterizing airway disease phenotypes, complementing medical expertise. However, comparing studies that derive phenotypes is challenging due to varying decisions made during phenotyping. We conducted a systematic review to describe studies that utilized unsupervised computational approaches for phenotyping obstructive airway diseases in children and adults.

Methods: We searched for relevant papers published between 2010 and 2020 in PubMed, EMBASE, Scopus, Web of Science, and Google Scholar. Additional sources included conference proceedings, reference lists, and expert recommendations. Two reviewers independently screened studies for eligibility, extracted data, and assessed study quality. Disagreements were resolved by a third reviewer. An in-house quality appraisal tool was used. Evidence was synthesized, focusing on populations, variables, and computational approaches used for deriving phenotypes.

Results: Of 120 studies included in the review, 60 focused on asthma, 19 on severe asthma, 28 on COPD, 4 on asthma-COPD overlap (ACO), and 9 on rhinitis. Among asthma studies, 31 focused on adults and 9 on children, with phenotypes related to atopy, age at onset, and disease severity. Severe asthma phenotypes were characterized by symptomatology, atopy, and age at onset. COPD phenotypes involved lung function, emphysematous changes, smoking, comorbidities, and daily life impairment. ACO and rhinitis phenotypes were mostly defined by symptoms, lung function, and sensitization, respectively. Most studies used hierarchical clustering, with some employing latent class modeling, mixture models, and factor analysis. The comprehensiveness of variable reporting was the best quality indicator, while reproducibility measures were often lacking.

Conclusion: Variations in phenotyping methods, study settings, participant profiles, and variables contribute to significant differences in characterizing asthma, severe asthma, COPD, ACO, and rhinitis phenotypes across studies. Lack of reproducibility measures limits the evaluation of computational phenotyping in airway diseases, underscoring the need for consistent approaches to defining outcomes and selecting variables to ensure reliable phenotyping.

Background: Aeroallergen sensitization is a major factor in asthma, and asthma is associated with impaired lung function. The independent association between sensitization and lung function is unclear.

Objectives: To examine factors associated with lung function in adolescence, with special interests in sensitization and asthma.

Methods: All schoolchildren in grade one and two (median age 8) in two municipalities in Northern Sweden were invited to a questionnaire survey of allergic diseases and skin prick tests to aeroallergens. This was repeated at ages 12 and, at 19 years also including spirometry and n = 1495 participated at all three occasions. Associations between risk factors and FEV1, FVC and FEV1/FVC were analysed by linear regression.

Results: Aeroallergen sensitization was not associated with lung function, irrespective of age at onset, type or degree of sensitization. Early-onset asthma, both persistent (B −0.35, 95% CI –0.60 to −0.09) and in remission (B −0.43, 95% CI –0.74 to −0.12) was associated with lower FEV1. Persistent asthma was associated with lower FEV1/FVC (B −0.81, 95% CI –1.07 to −0.55), and remission with lower FVC (B −0.37, 95% CI –0.67 to −0.70). No interaction between asthma and sensitization was found. Maternal smoking in pregnancy was associated with lower FEV1/FVC. Underweight at age 19 years was associated with lower FEV1 and FVC and overweight was associated with higher FEV1 and FVC, but lower FEV1/FVC.

Conclusions: Aeroallergen sensitization was not independently associated with lung function. Early onset asthma was strongly associated with lung function impairments in young adulthood and in sensitized and non-sensitized individuals alike.

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: Cigarette smoking stands as one of the leading causes of preventable death globally. Alternative tobacco products, such as e-cigarettes, have gained popularity due to the general perception of being less harmful. However, much is still unknown about the health implications of these novel products. In this study, we aimed to investigate if e-cigarettes could induce pulmonary inflammatory responses by measuring lung-related circulating extracellular vesicles (EVs) in the blood of healthy volunteers following brief e-cigarette vaping sessions, with and without nicotine.

Methods: 22 healthy volunteers were included. Employing a randomized, double-blind, cross-over design all participants vaped 30 puffs of e-cigarette aerosol, with and without nicotine, over a 30-min period. Blood samples were collected at baseline, 30- and 105-min following exposure. Lung-related EVs were quantified using flow cytometry. Analyzed markers included angiotensin converting enzyme (ACE), aldehyde dehydrogenase 3B1 (ALDH3B1), palate, lung and epithelial clone (PLUNC), complement component 3 (C3), C-C motif chemokine ligand 3 (CCL3), also known as macrophage inflammatory protein 1 alpha (MIP-1α), and uteroglobin, also known as club cell protein 16 (CC16). All these markers are associated with pulmonary inflammation.

Results: E-cigarette use, with nicotine but not without, resulted in a significant increase in three out of the six lung-related inflammatory markers measured and clear increases though not statistically significant in the remaining three.

Conclusion: The observed increase in levels of circulating lung-related inflammatory EV markers following vaping e-cigarette aerosol containing nicotine suggests that inhaled nicotine plays a central role in triggering pulmonary inflammation. Clinicaltrials.gov ID: NCT04175457.

Background: COPD is largely underdiagnosed. Active identification of cases is crucial to establish preventive measures before manifestation of clinical disease. The significance of different spirometric patterns preceding COPD, especially preserved ratio impaired spirometry (PRISm), has been highlighted but remains unclear.

Research Question: Which clinical characteristics, smoking habits, and spirometric patterns, with primary focus on PRISm findings, precede the development of airway obstruction (AO)?

Study Design and Methods: The OLIN COPD Study was established from 2002 through 2004. After re-examination of population-based cohorts, individuals with AO (n = 993; FEV1 to VC ratio < 0.70) were identified together with control participants without AO (n = 993; FEV1 to VC ratio ≥ 0.70). Most of these people had participated in examinations during the 1980s or 1990s, and in total, 902 cases and 819 control participants had previous clinical data. Logistic regression was performed with case status as outcome and spirometric patterns, age, sex, smoking habits, and BMI at first examination as covariates.

Results: The mean (SD) person-years between first examination and inclusion in the OLIN COPD Study was 10.5 (4.0) years. At first examination, the prevalence of PRISm was higher in cases (18.6%) vs control participants (13.4%). Current smoking was more common in cases (45.1% vs 18.2%), whereas former smoking was similar (31.8% vs 34.9%). Cases reported more respiratory symptoms (78.0% vs 44.3%) than control participants. At first examination, PRISm, current smoking, and former smoking were strongly associated with becoming a case when adjusted for confounders, with adjusted OR (aOR) of 3.5, 4.1, and 1.5, respectively. When stratifying for smoking habits, aORs for PRISm in those with current smoking, former smoking, and nonsmoking status were 2.9, 3.8 and 3.7, respectively.

Interpretation: In this study, PRISm was associated with transition into AO corresponding to COPD within 1 decade, independent of smoking habits and with similar strength of association among those who have never smoked, who formerly smoked, and who currently smoke.

Nickel allergy is common among children. The present study investigated prevalence trends of self-reported nickel allergy, risk factors, and atopic comorbidity among children. Eight-year-old children from Norrbotten County, Sweden, were recruited in 1996 (n = 3,430), 2006 (n = 2,585), and 2017 (n = 2,785). Self-reported nickel allergy decreased from 7.7% (2006) to 6.1% (2017; p = 0.024) and was significantly more common among girls. In 1996, only children with atopic dermatitis answered questions on nickel allergy. Among children with atopic dermatitis, no significant decrease was seen over the years 1996 to 2017. Ear piercing (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.39-2.68 and OR 5.57, 95% CI 3.71-8.38) and female sex (OR 4.05, 95% CI 2.68-6.13 and OR 1.73, 95% CI 1.09-2.74) were risk factors for self-reported nickel allergy in 2006 and 2017, respectively. Self-reported nickel allergy was significantly more prevalent among children with atopic dermatitis than without in 2006 (12.3% vs 6.4%; p < 0.001) and 2017 (11.5% vs 5.1%; p < 0.001), and among children with allergic rhinitis in 2017 (8.6% vs 4.7%; p = 0.015). In conclusion, we found a decreasing prevalence of self-reported nickel allergy, but not among children with atopic dermatitis. Ear piercing and female sex were strongly associated with nickel allergy. Our findings also suggest that nickel allergy is associated with atopic dermatitis and allergic rhinitis.