Background Heated tobacco products (HTPs) are increasingly popular alternative nicotine delivery systems. While marketed as lower-risk alternatives to combustible cigarettes, HTP aerosols still contain combustion byproducts. The acute systemic and pulmonary effects associated with these products have not yet been thoroughly examined. We aimed to evaluate the acute effects of HTP inhalation on the release of extracellular vesicles (EVs) bearing lung-specific and inflammatory biomarkers. Methods In a randomized, crossover study, 23 healthy occasional tobacco users underwent an active HTP exposure session (using an IQOS 3 Multi device) and a control session. Blood samples were collected at baseline and 4 hours post-exposure. Circulating EVs were isolated via ultracentrifugation and analyzed using flow cytometry. We quantified EVs expressing Angiotensin-Converting Enzyme (ACE), Aldehyde dehydrogenase 3B1 (ALDH3B1), Uteroglobin, Complement component 3 (C3), C-C motif chemokine ligand 3 (CCL3/MIP-1α), Palate lung and nasal epithelial clone protein (PLUNC), and Prolyl 4-hydroxylase beta (P4HB). Results Acute inhalation of HTP aerosols induced a statistically significant increase in circulating EVs expressing ACE, P4HB, C3, and CC16/Uteroglobin compared to the non-exposure control. A trend toward elevated ALDH3B1 expression was observed, while levels of CCL3 and PLUNC remained unchanged. Conclusion Acute exposure to HTPs triggers a rapid release of EVs associated with cellular stress, pulmonary injury, and pro-inflammatory responses. Increases in biomarkers such as ACE, C3, and the cancer-associated protein P4HB indicate that HTPs could impair lung health and initiate pro-thrombotic and pro-inflammatory cascades, supporting the need for more stringent regulatory controls.

INTRODUCTION:Tests for dog and cat allergen molecules might be useful to characterize individuals with clinical symptoms in unselected population samples. The aim of this study was to present prevalence data and to investigate airway symptoms to cats and dogs in relation to sensitization to cat and dog allergen molecules. METHODS:In a random sample from a population-based cohort aged 19 years, 595 subjects were tested for sensitization to airborne allergens. Sera from subjects with IgE levels of >0.10 kU/L to cat, dog, or horse were further analyzed by microarray (ImmunoCAP™ ISAC 112) for dog molecules Can f 1-6 and cat molecules Fel d 1, 2, and 4. Fel d 7 was analyzed with ImmunoCAP™. Information about symptoms of asthma and rhinoconjunctivitis upon cat and dog exposure was obtained by a structured interview. RESULTS:The most prevalent (51.6%) sensitizing dog allergen molecule was Can f 5. The prevalence of asthma upon dog contact increased from 0.9% in individuals negative to all tested dog molecules to 40% in individuals sensitized to 6 dog molecules. The prevalence of asthma upon dog contact was related to the number of dog lipocalin sensitizations independent of sensitization to Can f 5, whereas for rhinoconjunctivitis Can f 5 co-sensitization played a role. The most prevalent (91.2%) sensitizing cat molecule was Fel d 1 and co-sensitization to up to three molecules increased the prevalence of asthma when exposed to cat. CONCLUSION:In individuals sensitized to cat as in individuals sensitized to dog, the prevalence of allergic symptoms increased with the number of sensitizing allergen molecules. Individuals sensitized to dog had more complex sensitization patterns to allergen molecules compared to those sensitized to cat. Asthma upon dog exposure was mostly associated with dog lipocalin sensitization, whereas Can f 5 sensitization increased the risk of rhinoconjunctivitis.

Abstract In asthma, suboptimal disease control is common due to limited knowledge about self-management, undertreatment and infrequent follow-up visits. Most patients are treated in primary care where asthma/COPD clinics (ACC) are recommended in Sweden, but evidence of the effects is limited. The aim was to compare certified ACCs with clinics providing regular care in terms of adherence to asthma management guidelines, and the associations with asthma symptom control, healthcare consumption, and mortality in adults with asthma. In this cohort study, we extracted data from the Swedish National Airway Register, on 84230 adults with asthma, cared for at certified ACCs (n = 17 primary care centres) and regular care clinics (n = 650 primary care centres) in Sweden. Data were linked to other national registers in order to obtain data about pharmaceuticals, healthcare consumption, and mortality. The index date was the years 2015–2017, and the study ended in 2022. A binary logistic regression was used to assess morbidity and mortality associations at the study’s end. A higher proportion of patients at certified ACCs received interventions such as patient education, written asthma action plan, smoking cessation, Asthma Control Test, spirometry, and inhaled corticosteroids than patients at regular care clinics. Certified ACCs were associated with a lower probability of uncontrolled asthma (OR 0.76, 95% CI 0.67–0.87), need of specialist/emergency care (OR 0.69, 95% CI 0.51–0.92) and death (OR 0.69, 95% CI 0.55–0.86). In conclusion, adherence to asthma management guidelines was higher in certified ACCs which were associated with a more well-controlled asthma, less secondary healthcare visits and lower all-cause mortality, but not with frequent exacerbations. Our findings highlight the importance of ACCs in providing evidence-based care in accordance with asthma management guidelines.

Background:Longitudinal data on weight change, its timing, and the age of obesity onset in relation to cause-specific mortality are limited. Methods:From ODDS, a nationwide pooled cohort study in Sweden, we included 258,269 men and 361,784 women with at least three weight assessments between ages 17 and 60, collected in 1963-2015. We applied linear mixed-effects models to estimate weight trajectories, age of obesity onset, and age-specific weight changes between ages 17 and 60. Outcomes were all-cause and cause-specific mortality, assessed from 5 years after the last weight assessment until death, emigration, or 31 December 2020. Associations with mortality were calculated using multivariable Cox regression models. Findings:Over a median follow-up of 23.3 years in men and 11.7 years in women, 86,673 men and 29,076 women died. The median weight change between ages 17 and 60 was 0.42 kg/year in both sexes. A steep weight gain trajectory over this period, early obesity onset, and high weight gain between ages 17 and 29 were associated with higher all-cause mortality and with 13 of 23 specific causes of death investigated in men and 12 of 19 in women. Affected causes included cardiovascular diseases (including most subtypes), cancer (including specific types), type 2 diabetes, and digestive and genitourinary diseases. Hazard ratios (95% confidence intervals) of all-cause mortality associated with obesity onset at ages 17-29 vs. never by age 60 were 1.69 (1.60-1.79) in men and 1.71 (1.55-1.88) in women; and per 0.5 kg/year weight change at ages 17-29, 1.18 (1.17-1.19) and 1.16 (1.14-1.18), respectively. Weight gain later in adulthood generally showed weaker associations, except for cancer mortality in women, where the association was similar to that observed with earlier weight gain. Interpretation:Weight gain in adulthood, especially in young adulthood, and obesity onset before age 30 are strong risk factors for mortality from multiple non-communicable diseases, underscoring the importance of early obesity prevention. Future studies should incorporate richer confounding data and, ideally, measures of changes in central adiposity and muscle mass. Funding:The Swedish Research Council, Swedish Cancer Society, Crafoord Foundation, Malmö General Hospital Cancer Foundation, and the Swedish Foundation for Strategic Research.

BACKGROUND:Obesity assessed at a single time point in adulthood has shown no consistent association with prostate cancer (PCa) incidence but has been positively associated with PCa death. We investigated the association of total and age-specific adult weight trajectories with PCa aggressiveness and death. METHODS:We analyzed data from 258,494 men in Sweden with at least 3 weight observations between ages 17 and 60. Individual weight trajectories were estimated using linear mixed-effects models with natural cubic and linear splines for age, incorporating random intercepts and slopes. These estimates were included in multivariable-adjusted Cox proportional hazards models. RESULTS:Over a median follow-up of 25 years, 22 055 men were diagnosed with PCa and 4547 died from the disease. Steep weight gain was inversely associated with PCa diagnosed during the PSA testing era (1997 onwards) and via asymptomatic PSA testing, but not with aggressive PCa. Among men with PCa, steep weight gain was associated with increased risk of PCa death (HR quintile 5 vs. 1 = 1.23, 95% CI = 1.08 to 1.40), primarily driven by weight gain between ages 45 and 60 (HR per 1 kg/year = 1.31, 95% CI = 1.10 to 1.57). CONCLUSIONS:The associations observed for incident PCa appear to be influenced by PSA testing uptake; however, the extent to which detection bias contributes remains uncertain. Conversely, late midlife weight gain was associated with an elevated risk of PCa death, underscoring the importance of weight management during this period as a potentially modifiable factor for reducing PCa death.

The use of electronic nicotine delivery systems, such as e-cigarettes and heated tobacco products (HTPs), is increasing, but knowledge of their short and long-term toxicological effects remains limited. Here, aerosols generated from an e-cigarette using a flavour-free e-liquid base, both with and without nicotine, an HTP, and a conventional cigarette were characterised for the production of polycyclic aromatic hydrocarbons (PAHs), carbonyls and volatile organic compounds (VOCs). Furthermore, extracts from vapour and smoke were generated, and their acute toxicity was assessed in human lung epithelial cells and fibroblasts. Cigarette smoke contained significantly more toxic compounds and induced the highest degree of toxicity in all the tested cell lines, followed by the HTP, and then the nicotine containing e-cigarette. Notably, the nicotine containing e-cigarette produced similar levels of formaldehyde as the HTP and cigarette smoke, and caused a greater decrease in cell viability in primary lung fibroblasts compared to the nicotine-free e-cigarette. Although the HTP aerosol contained lower levels of toxicants than cigarette smoke, some VOCs specific to HTPs were detected. More independent research is needed to identify toxicant-specific production in emerging nicotine delivery systems and their potential health impacts to better inform policy makers, health care providers and the general public.

Purpose:Asthma control is multifaceted, involving symptoms and risk of adverse outcomes. Emerging evidence suggests a bidirectional link between poor asthma control and severe COVID-19, but large studies addressing all components of asthma control in this context are lacking. Our aims were to evaluate if 1) uncontrolled asthma was a risk factor for COVID-19 hospitalization and death, 2) asthma control changed during the pandemic and 3) COVID-19 hospitalization was a risk factor for future uncontrolled asthma. Methods:Patients with asthma (n = 125,362) were identified in the Swedish National Airway Register from January 2014 to 2020, whereof n = 2377 were hospitalized and n = 305 died due to COVID-19 during follow-up until December 2022. Asthma control was evaluated by symptoms (Asthma Control Test (ACT) ≥ 20: well controlled, ACT 16-19 not well-controlled and ACT < 16 very poorly controlled asthma), lung function (FEV1% predicted (pp)) and frequent and/or severe exacerbations (dispensed oral corticosteroids and asthma inpatient care). Results:ACT 16-19 (RR 1.57, 95% CI 1.34-1.84), ACT < 16 (1.72, 1.46-2.02), FEV1 < 80pp (1.29, 1.13-1.48), frequent (1.99, 1.79-2.21) and severe exacerbations (2.54, 2.09-3.08) were associated with a higher risk for COVID-19 hospitalization. COVID-19 death was associated with ACT < 16, frequent and severe exacerbations. Overall, at follow-up, proportions of ACT < 20 (36.1%) and FEV1 < 80pp (48.3%) were stable, while exacerbations decreased (frequent; 7.9% to 6.8%, severe; 1.3% to 0.4%). COVID-19 hospitalization was a risk factor for frequent (1.35, 1.22-1.51) and severe (3.42, 1.22-1.51) future asthma exacerbations. Conclusion:All dimensions of poor asthma control were associated with an increased risk of severe COVID-19. In contrast, only exacerbation risk was elevated following COVID-19.

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.

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. 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. 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. 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.

Aims: To study the importance of decreasing tobacco smoking on the occurrence of larynx cancer in men and women.Methods: The incidence rates of larynx cancer in the Swedish population between 1970 and 2021 were retrieved from the Swedish Cancer Register for ages 50-84 years, stratified for sex, age and calendar year. Data on the population's smoking habits was retrieved from surveys and from taxation on the sale of cigarettes. The occurrence of larynx cancer was compared to smoking habits, sex and age. The time trends were compared between larynx and lung cancer.Results: Over the years, Swedish men and women have had different smoking habits, especially older persons during the 1970s. In 1963, the prevalence of current smokers in women 50-69 years was 11%, while it was 46% in men. Around 2020, less than 10% of men and women in all age groups were current smokers. However, men had higher incidence rates of larynx cancer than women, even when their smoking habits were similar. For example, men and women 60-64 years of age in 2017-2021 had similar smoking habits during their life but the relative risk of larynx cancer in men compared to women was 3.3 (95% CI 1.7-4.8). However, pipe smoking was much more common in men.Conclusions: The study indicates that other causes than cigarette smoking have an impact on the occurrence of larynx cancer in Sweden. Pipe smoking and occupational exposure to carcinogenic materials such as asbestos may be underlying causes of the difference in cancer risk between Swedish men and women.

Chronic Obstructive Pulmonary disease (COPD) is largely underdiagnosed. Active case finding 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 is still unclear. Which clinical characteristics, smoking habits and spirometric patterns, with primary focus on PRISm, precede the development of airway obstruction? The OLIN COPD COPD Study was established in 2002-04. After re-examinations of population-based cohorts, individuals with airway obstruction (AO) (n=993 cases, FEV1/VC<0.70) were identified together with non-obstructive controls (n=993, FEV1/VC≥0.70). The majority of these had participated in examinations during the 1980s or 1990s and in total 902 cases and 819 controls had previous clinical data. Logistic regression was performed with case as outcome and spirometric patterns, age, sex, smoking habits and body mass index (BMI) at first examination as covariates. The mean person-years between first examination and inclusion in the OLIN COPD COPD study was 10.5±4.0y. At first examination, the prevalence of PRISm was higher in cases (18.6%) vs controls (13.4%). Current smoking was more common in cases (45.1% vs 18.2%), while former smoking was similar (31.8 vs. 34.9%). Cases reported more respiratory symptoms (78.0 vs. 44.3%) than controls. 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 current smokers, former smokers and non-smokers were 2.9, 3.8 and 3.7, respectively. PRISm associated with transition into airway obstruction corresponding to COPD within a decade, independent of smoking habits and with similar strength of association among non-, former and current smokers.

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: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: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.