All-cause and cause-specific mortality by spirometric pattern and sex - a population-based cohort study.

BACKGROUND: Chronic airway obstruction (CAO) and restrictive spirometry pattern (RSP) are associated with mortality, but sex-specific patterns of all-cause and specific causes of death have hardly been evaluated. OBJECTIVES: To study the possible sex-dependent differences of all-cause mortality and patterns of cause-specific mortality among men and women with CAO and RSP, respectively, to that of normal lung function (NLF). DESIGN: Population-based prospective cohort study. METHODS: Individuals with CAO [FEV1/vital capacity (VC) < 0.70], RSP [FEV1/VC ⩾ 0.70 and forced vital capacity (FVC) < 80% predicted] and NLF (FEV1/VC ⩾ 0.70 and FVC ⩾ 80% predicted) were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-2004. Mortality data were collected through April 2016, totally covering 19,000 patient-years. Cox regression and Fine-Gray regression accounting for competing risks were utilized to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, body mass index, sex, smoking habits and pack-years. RESULTS: The adjusted hazard for all-cause mortality was higher in CAO and RSP than in NLF (HR, 95% CI; 1.69, 1.31-2.02 and 1.24, 1.06-1.71), and the higher hazards were driven by males. CAO had a higher hazard of respiratory and cardiovascular death than NLF (2.68, 1.05-6.82 and 1.40, 1.04-1.90). The hazard of respiratory death was significant in women (3.41, 1.05-11.07) while the hazard of cardiovascular death was significant in men (1.49, 1.01-2.22). In RSP, the higher hazard for respiratory death remained after adjustment (2.68, 1.05-6.82) but not for cardiovascular death (1.11, 0.74-1.66), with a similar pattern in both sexes. CONCLUSION: The higher hazard for all-cause mortality in CAO and RSP than in NLF was male driven. CAO was associated with respiratory death in women and cardiovascular death in men, while RSP is associated with respiratory death, similarly in both sexes.

All-cause and cause specific mortality in relation to different lung function patterns and sex; normal, obstructive and restricted lung functionChronic airway obstruction and restrictive spirometry pattern are associated with mortality, but sex specific patterns have hardly been evaluated.Aim: To study possible sex-dependent differences of all-cause and cause-specific mortality among men and women with chronic airway obstruction and restrictive spirometry pattern, respectively, compared to that of normal lung function.Methods: Individuals with chronic airway obstruction, restrictive spirometry pattern and normal lung function were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-04. Mortality data were collected through April 2016, totally covering 19,000 patient-years of observation time. We analyzed the Hazard Ratios for all-cause and cause-specific death comparing chronic airway obstruction and restrictive spirometry pattern to that of normal lung function, adjusting for age, body mass index, sex, smoking habits and pack-years. Similar analyses were conducted separately for men and women.Results: The hazard for all-cause mortality was higher in both chronic airway obstruction and restrictive spirometry pattern than in normal lung function and, the higher hazards were male-driven. In chronic airway obstruction the hazard of respiratory and cardiovascular deaths higher than in those with normal lung function. The increased hazard of respiratory death was significant in women while the increased hazard of cardiovascular death was significant in men. In restrictive spirometry pattern, the higher hazard for respiratory but not cardiovascular death persisted after adjustment, similarly in both sexes.Conclusions: The higher hazard for all-cause mortality in chronic airway obstruction and restrictive spirometry pattern than in normal lung function was male-driven. Chronic airway obstruction associated with respiratory death in women and cardiovascular death in men, while restrictive pattern associated with respiratory death, similarly in both sexes.

Level of Education Modifies Asthma Mortality in Norway and Sweden. The Nordic EpiLung Study.

Background and Aim: The relationship between socioeconomic status (SES), asthma and mortality is complex and multifaceted, and it is not established if educational level modifies the association between asthma and mortality. The aim was to study the association between asthma and mortality in Sweden and Norway and to what extent educational level modifies this association. Participants and Methods: Within the Nordic EpiLung Study, >56,000 individuals aged 30-69 years participated in population-based surveys on asthma and associated risk factors in Sweden and Norway during 2005-2007. Data on educational level and 10-year all-cause mortality were linked by national authorities. The fraction of mortality risk attributable to asthma was calculated, and Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for mortality related to asthma, stratified by educational level. Results: In total, 5.5% of all deaths was attributed to asthma. When adjusted for potential confounders, the HR for mortality related to asthma was 1.71 (95% CI 1.52-1.93). Those with primary level of education had higher hazard of all-cause death related to asthma than those with tertiary level (HR 1.80, 95% CI 1.48-2.18, vs HR 1.39, 95% CI 0.99-1.95). Conclusion: Asthma was associated with an overall 71% increased all-cause mortality and 5.5% of deaths can be attributed to asthma. Educational levels modified the risk of mortality associated with asthma, with the highest risk among those with primary education.

Electronic cigarette use in relation to changes in smoking status and respiratory symptoms.

INTRODUCTION: How e-cigarette use relates to changes in smoking status and respiratory symptoms in the population remains controversial. The aim was to study the association between e-cigarette use and, changes in smoking status and changes in respiratory symptoms. METHODS: A prospective, population-based study of random samples of the population (age 16-69 years) was performed within The Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). A validated postal questionnaire containing identical questions was used in OLIN and WSAS at baseline in 2006-2008 and at follow-up in 2016. In total, 17325 participated on both occasions. Questions about respiratory symptoms and tobacco smoking were included in both surveys, while e-cigarette use was added in 2016. RESULTS: In 2016, 1.6% used e-cigarettes, and it was significantly more common in persistent tobacco smokers (10.6%), than in those who quit smoking (2.1%), started smoking (7.8%), or had relapsed into tobacco smoking at follow-up (6.4%) (p<0.001). Among current smokers at baseline, tobacco smoking cessation was less common in e-cigarette users than e-cigarette non-users (14.2% vs 47.6%, p<0.001) and there was no association with a reduction in the number of tobacco cigarettes smoked per day. Those who were persistent smokers reported increasing respiratory symptoms. In contrast, the symptoms decreased among those who quit tobacco smoking, but there was no significant difference in respiratory symptoms between quitters with and without e-cigarette use. CONCLUSIONS: E-cigarette use was associated with persistent tobacco smoking and reporting respiratory symptoms. We found no association between e-cigarette use and tobacco smoking cessation, reduction of number of tobacco cigarettes smoked per day or reduction of respiratory symptoms.

Topical Hydroquinone for Hyperpigmentation: A Narrative Review.

Topical hydroquinone (HQ) has been used for decades to treat disorders of hyperpigmentation such as melasma, post-inflammatory hyperpigmentation, and solar lentigines. Additionally, it has been used as a skin-lightening agent for cosmetic purposes. Multiple studies have shown it to be effective in treating hyperpigmentation, though it is not without side effects. Currently, HQ is not approved for over-the-counter use in the United States. Its use is also banned in other countries, including Japan, Australia, and the European Union. Hyperpigmentation disorders affect individuals worldwide. Patients with these disorders are frequently seen in medical practices. Hyperpigmentation disorders can significantly negatively impact a person's quality of life, and agents that treat hyperpigmentation can improve patient outcomes. A comprehensive literature search was performed on HQ as a treatment for skin hyperpigmentation disorders. A literature review revealed that HQ is an effective compound for treating hyperpigmentation disorders and can be combined with other therapies for enhanced results. Evidence exists to support HQ as a topical therapy for skin hyperpigmentation. HQ is not without side effects and should be prescribed by trained professionals who can educate patients on usage. HQ can be used in pharmaceutical regimens to treat hyperpigmentation disorders.

Severity of adult-onset asthma - a matter of blood neutrophils and severe obesity.

BACKGROUND: Adult-onset asthma is associated with a poor treatment response. The aim was to study associations between clinical characteristics, asthma control and treatment in adult-onset asthma. METHODS: Previous participants within the population-based Obstructive Lung Disease in Northern Sweden studies (OLIN) were in 2019-2020 invited to clinical examinations including structured interviews, spirometry, fractional exhaled nitric oxide (FeNO), skin prick test and blood sampling. In total, n = 251 individuals with adult-onset asthma (debut >15 years of age) were identified. Uncontrolled asthma was defined according to ERS/ATS and treatment step according to GINA (2019). RESULTS: Among individuals with uncontrolled asthma (34%), severe obesity (16.3% vs 7.9%, p = 0.041) and elevated levels of blood neutrophils, both regarding mean level of blood neutrophils (4.25*109/L vs 3.67*109/L, p = 0.003), and proportions with ≥4*109/L (49.4% vs 33.3%, p = 0.017) and ≥5*109/L (32.1% vs 13.7%, p < 0.001) were more common than among those with controlled asthma. Adding the dimension of GINA treatment step 1-5, individuals with uncontrolled asthma on step 4-5 treatment had the highest proportions of blood neutrophils ≥5*109/L (45.5%), severe obesity (BMI≥35, 26.1%), dyspnea (mMRC≥2) (34.8%), and most impaired lung function in terms of FEV1%<80% of predicted (42.9%), FEV1

Phenotyping asthma with airflow obstruction in middle-aged and older adults: a CADSET clinical research collaboration.

BACKGROUND: The prevalence and clinical profile of asthma with airflow obstruction (AO) remain uncertain. We aimed to phenotype AO in population- and clinic-based cohorts. METHODS: This cross-sectional multicohort study included adults ≥50 years from nine CADSET cohorts with spirometry data (N=69 789). AO was defined as ever diagnosed asthma with pre-BD or post-BD FEV1/FVC <0.7 in population-based and clinic-based cohorts, respectively. Clinical characteristics and comorbidities of AO were compared with asthma without airflow obstruction (asthma-only) and chronic obstructive pulmonary disease (COPD) without asthma history (COPD-only). ORs for comorbidities adjusted for age, sex, smoking status and body mass index (BMI) were meta-analysed using a random effects model. RESULTS: The prevalence of AO was 2.1% (95% CI 2.0% to 2.2%) in population-based, 21.1% (95% CI 18.6% to 23.8%) in asthma-based and 16.9% (95% CI 15.8% to 17.9%) in COPD-based cohorts. AO patients had more often clinically relevant dyspnoea (modified Medical Research Council score ≥2) than asthma-only (+14.4 and +14.7 percentage points) and COPD-only (+24.0 and +5.0 percentage points) in population-based and clinic-based cohorts, respectively. AO patients had more often elevated blood eosinophil counts (>300 cells/µL), although only significant in population-based cohorts. Compared with asthma-only, AO patients were more often men, current smokers, with a lower BMI, had less often obesity and had more often chronic bronchitis. Compared with COPD-only, AO patients were younger, less often current smokers and had less pack-years. In the general population, AO patients had a higher risk of coronary artery disease than asthma-only and COPD-only (OR=2.09 (95% CI 1.26 to 3.47) and OR=1.89 (95% CI 1.10 to 3.24), respectively) and of depression (OR=1.41 (95% CI 1.19 to 1.67)), osteoporosis (OR=2.30 (95% CI 1.43 to 3.72)) and gastro-oesophageal reflux disease (OR=1.68 (95% CI 1.06 to 2.68)) than COPD-only, independent of age, sex, smoking status and BMI. CONCLUSIONS: AO is a relatively prevalent respiratory phenotype associated with more dyspnoea and a higher risk of coronary artery disease and elevated blood eosinophil counts in the general population compared with both asthma-only and COPD-only.

Age-related differences in associations between uncontrolled asthma, comorbidities and biomarkers in adult-onset asthma.

OBJECTIVE: Adult-onset asthma is a recognized but heterogeneous phenotype and has been described to associate with poor asthma control. Knowledge about associations between clinical characteristics including comorbidities and control of adult-onset asthma is limited, especially in older populations. We aimed to study how clinical biomarkers and comorbidities are associated with uncontrolled asthma among middle-aged and older individuals with adult-onset asthma. METHODS: Clinical examinations including structured interview, asthma control test (ACT), spirometry, skin prick test (SPT), blood sampling, and measurement of exhaled fractional nitric oxide (FeNO) was performed in a population-based adult-onset asthma cohort in 2019-2020 (n = 227, 66.5% female). Analyses were performed among all included, and separately in middle-aged (37-64 years, n = 120) and older (≥65 years, n = 107) participants. RESULTS: In bivariate analysis, uncontrolled asthma (ACT ≤ 19) was significantly associated with a blood neutrophil count ≥5/µl, BMI ≥30, and several comorbidities. In multivariable regression analysis, uncontrolled asthma was associated with neutrophils ≥5/µl (OR 2.35; 95% CI 1.11-4.99). In age-stratified analysis, BMI ≥30 (OR 3.04; 1.24-7.50), eosinophils ≥0.3/µl (OR 3.17; 1.20-8.37), neutrophils ≥5/µl (OR 4.39; 1.53-12.62) and allergic rhinitis (OR 5.10; 1.59-16.30) were associated with uncontrolled asthma among the middle-aged. Among the older adults, uncontrolled asthma was only associated with comorbidities: chronic rhinitis (OR 4.08; 1.62-10.31), ischemic heart disease (OR 3.59; 1.17-10.98), malignancy (OR 3.10; 1.10-8.73), and depression/anxiety (OR 16.31; 1.82-146.05). CONCLUSIONS: In adult-onset asthma, comorbidities were strongly associated with uncontrolled asthma among older adults, while clinical biomarkers including eosinophils and neutrophils in blood were associated with uncontrolled asthma among middle-aged.

Underdiagnosis and misclassification of COPD in Sweden - A Nordic Epilung study.

INTRODUCTION: The prevalence of COPD tends to level off in populations with decreasing prevalence of smoking but the extent of underdiagnosis in such populations needs further investigation. AIM: To investigate underdiagnosis and misclassification of COPD with a focus on socio-economy, lifestyle determinants and healthcare utilization. METHOD: The 1839 participants were selected from two ongoing large-scale epidemiological research programs: The Obstructive Lung Disease in Northern Sweden Studies and the West Sweden Asthma Study. COPDGOLD was defined according to the fixed post-bronchodilator spirometric criteria FEV1/FVC<0.70 in combination with respiratory symptoms. RESULTS: Among the 128 participants who fulfilled the criteria for COPDGOLD, the underdiagnosis was 83.6% (n = 107) of which 57.9% were men. The undiagnosed participants were younger, had higher FEV1% of predicted and less frequently a family history of bronchitis. One in four of the undiagnosed had utilized healthcare and had more frequently utilized healthcare due to a burden of respiratory symptoms than the general population without COPD. Underdiagnosis was not related to educational level. Misclassification of COPD was characterized by being a woman with low education, ever smoker, having respiratory symptoms and having a previous asthma diagnosis. CONCLUSION: In the high income country Sweden, the underdiagnosis of COPD was highly prevalent. Reduced underdiagnosis can contribute to risk factor modification, medical treatment and self-management strategies in early stages of the disease, which may prevent disease progression and improve the quality of life among those affected. Therefore, there is a need to increase the use of spirometry in primary care to improve the diagnostic accuracy.

Lung Function Trajectories and Associated Mortality among Adults with and without Airway Obstruction.

Rationale: Spirometry is essential for diagnosis and assessment of prognosis in patients with chronic obstructive pulmonary disease (COPD). Objectives: To identify FEV1 trajectories and their determinants on the basis of annual spirometry measurements among individuals with and without airway obstruction (AO) and to assess mortality in relation to trajectories. Methods: From 2002 through 2004, individuals with AO (FEV1/VC < 0.70, n = 993) and age- and sex-matched nonobstructive (NO) referents were recruited from population-based cohorts. Annual spirometry until 2014 was used in joint-survival latent-class mixed models to identify lung function trajectories. Mortality data were collected during 15 years of follow-up. Measurements and Main Results: Three trajectories were identified among the subjects with AO and two among the NO referents. Trajectory membership was driven by baseline FEV1% predicted (FEV1%pred) in both groups and also by pack-years in subjects with AO and current smoking in NO referents. Longitudinal FEV1%pred depended on baseline FEV1%pred, pack-years, and obesity. The trajectories were distributed as follows: among individuals with AO, 79.6% in AO trajectory 1 (FEV1 high with normal decline), 12.8% in AO trajectory 2 (FEV1 high with rapid decline), and 7.7% in AO trajectory 3 (FEV1 low with normal decline) (mean, 27, 72, and 26 ml/yr, respectively) and, among NO referents, 96.7% in NO trajectory 1 (FEV1 high with normal decline) and 3.3% in NO trajectory 2 (FEV1 high with rapid decline) (mean, 34 and 173 ml/yr, respectively). Hazard for death was increased for AO trajectories 2 (hazard ratio [HR], 1.56) and 3 (HR, 3.45) versus AO trajectory 1 and for NO trajectory 2 (HR, 2.99) versus NO trajectory 1. Conclusions: Three different FEV1 trajectories were identified among subjects with AO and two among NO referents, with different outcomes in terms of FEV1 decline and mortality. The FEV1 trajectories among subjects with AO and the relationship between low FVC and trajectory outcome are of particular clinical interest.

Obesity associates with increased all-cause and cardiovascular mortality in adults with asthma.

BACKGROUND: Asthma and obesity are prevalent conditions that are increasing worldwide. Asthma is characterized by airway inflammation and bronchial variability, while obesity is a complex metabolic disorder that poses significant morbidity and mortality risks. Obesity is a risk factor for asthma and a plethora of other non-communicable diseases. OBJECTIVE: To compare all-cause and cause-specific mortality between obese, overweight and normal weight adults with asthma in a cohort with long-term follow-up. METHODS: Individuals from a population-based adult asthma cohort recruited in Norrbotten county, Sweden, were clinically examined between 1986 and 2001 and grouped into body mass index (BMI) categories. Underlying causes of death until December 31st, 2020 were categorized as cardiovascular, respiratory, cancer and other mortality by linking cohort data to the Swedish National Board of Health and Welfare's National Cause of Death register. Hazard ratios (HR) with 95% confidence intervals (CI) for all-cause and cause-specific mortality associated with overweight and obesity were calculated via Cox proportional hazard models. RESULTS: In total, 940 individuals were normal weight, 689 overweight and 328 obese while only 13 were underweight. Obesity increased the hazard for all-cause (HR 1.26, 95% CI 1.03-1.54) and cardiovascular mortality (HR 1.43, 95% CI 1.03-1.97). Obesity was not significantly associated with respiratory or cancer mortality. Overweight did not increase the hazard of all-cause or any cause-specific mortality category. CONCLUSION: Obesity, but not overweight, was significantly associated with increased hazard of all-cause and cardiovascular mortality in adults with asthma. Neither obesity nor overweight were associated with increased hazard of respiratory mortality.

Multiple manifestations of uncontrolled asthma increase the risk of severe COVID-19.

OBJECTIVE: Asthma control is of importance when assessing the risk of severe outcomes of COVID-19. The aim of this study was to explore associations of clinical characteristics and the effect of multiple manifestations of uncontrolled asthma with severe COVID-19. METHODS: In 2014-2020, adult patients with uncontrolled asthma, defined as Asthma Control Test (ACT) ≤19 were identified in the Swedish National Airway Register (SNAR) (n = 24533). The SNAR database, including clinical data, was linked with national registers to identify patients with severe COVID-19 (n = 221). The effect of multiple manifestations of uncontrolled asthma was based on: 1) ACT ≤15, 2) frequent exacerbations and 3) previous asthma inpatient/secondary care and evaluated stepwise. Poisson regression analyses were conducted with severe COVID-19 as the dependent variable. RESULTS: In this cohort with uncontrolled asthma, obesity was the strongest independent risk factor for severe COVID-19 in both sexes, but even greater in men. Multiple manifestations of uncontrolled asthma were more common among those with severe COVID-19 vs. without: one, 45.7 vs. 42.3%, two, 18.1 vs. 9.1% and three, 5.0 vs. 2.1%. The risk ratio (RR) of severe COVID-19 increased with an increasing number of manifestations of uncontrolled asthma: one, RR 1.49 (95% CI 1.09-2.02), two, RR 2.42 (95% CI 1.64-3.57) and three, RR 2.96 (95% CI 1.57-5.60), when adjusted for sex, age, and BMI. CONCLUSIONS: It is important to consider the effect of multiple manifestations of uncontrolled asthma and obesity when assessing patients with COVID-19, as this increases the risk of severe outcomes substantially.

Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry.

Rationale: Postbronchodilator spirometry is used for the diagnosis of chronic obstructive pulmonary disease. However, prebronchodilator reference values are used for spirometry interpretation. Objectives: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or postbronchodilator reference values generated within SCAPIS (Swedish CArdioPulmonary bioImage Study) when interpreting postbronchodilator spirometry in a general population. Methods: SCAPIS reference values for postbronchodilator and prebronchodilator spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or postbronchodilator reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). Measurements and Main Results: Bronchodilation resulted in higher predicted medians and lower limits of normal (LLNs) for FEV1/FVC ratios. The prevalence of postbronchodilator FEV1/FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV1/FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV1/FVC ratio, and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%; P < 0.001), and self-reported physician-diagnosed chronic obstructive pulmonary disease (2.8% vs. 0.5%, P < 0.001) than subjects with a postbronchodilator FEV1/FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of postbronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using postbronchodilator reference values when interpreting postbronchodilator spirometry might enable the identification of individuals with mild disease and be clinically relevant.

Postural control among individuals with and without chronic obstructive pulmonary disease: A cross-sectional study of motor and sensory systems.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is considered a heterogenic syndrome with systemic effects, including muscle dysfunction. There is evidence of postural control impairments among individuals with COPD, partly related to muscle weakness. However, research is scarce regarding the other underlying systems of postural control, such as the visual, somatosensory and vestibular system. The aim was to compare postural control, as well as the motor and sensory systems, between individuals with and without COPD. METHODS: Twenty-two participants with COPD (mean age 74.0 ±6.2 years) and 34 non-obstructive references (mean age 74.9 ±4.9 years) participated in this cross-sectional study. Postural control was assessed with center of pressure trajectory of postural sway in quiet as well as a limits of stability test, calculating mediolateral and anteroposterior amplitudes for each test. Assessment of function in the motor system included maximum hand grip strength, as well as maximum strength in muscles around the hip, knee and ankle joints. Visual acuity, pressure sensibility, proprioception, vestibular screening, and reaction time were also included. Data was compared between groups, and significant differences in postural control were further analyzed with an orthogonal projection of latent structures regression model. RESULTS: There was a significantly increased sway amplitude in the mediolateral direction in quiet stance on soft surface with eyes open (p = 0.014) as well as a smaller anteroposterior amplitude in the limits of stability test (p = 0.019) in the COPD group. Regression models revealed that the mediolateral amplitude was related to visual acuity and the burden of tobacco smoking assessed as pack-years. Further, muscle strength associated with anteroposterior amplitude in limits of stability test in the COPD group, and with age and ankle dorsal flexion strength among the referents. Besides for lower ankle plantar flexion strength in the COPD group, there were however no significant differences in muscle strength. CONCLUSIONS: Individuals with COPD had a decreased postural control and several factors were associated with the impairments. The findings imply that the burden of tobacco smoking and reduced visual acuity relate to increased postural sway in quiet stance, and that muscle weakness is related to decreased limits of stability, among individuals with COPD.

Exacerbation Risk and Mortality in Global Initiative for Chronic Obstructive Lung Disease Group A and B Patients with and without Exacerbation History.

Rationale: Risk stratification of patients according to chronic obstructive pulmonary disease severity is clinically important and forms the basis of therapeutic recommendations. No studies have examined the association for Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and group B patients with (A1 and B1, respectively) and without (A0 and B0, respectively) an exacerbation in the past year with future exacerbations, hospitalizations, and mortality in perspective with the new GOLD ABE classification. Objectives: The aim was to examine the association between GOLD A0, A1, B0, B1, and E patients and future exacerbations, respiratory and cardiovascular hospitalizations, and mortality. Methods: In this nationwide cohort study, we identified patients with a diagnosis of chronic obstructive pulmonary disease, aged ⩾30 years, and registered in the Swedish National Airway Register between January 2017 and August 2020. Patients were stratified in GOLD groups A0, A1, B0, B1, and E and were followed until January 2021 for exacerbations, hospitalizations, and mortality in national registries. Measurements and Main Results: The 45,350 eligible patients included 25% A0, 4% A1, 44% B0, 10% B1, and 17% E. Moderate exacerbations, all-cause and respiratory hospitalizations, and all-cause and respiratory mortality increased by GOLD group A0-A1-B0-B1-E, except for moderate exacerbations, which were higher in A1 than in B0. Group B1 had a substantially higher hazard ratio for future exacerbation (2.56; 95% confidence interval [95% CI] 2.40-2.74), all-cause hospitalization (1.28; 1.21-1.35), and respiratory hospitalization (1.44; 1.27-1.62), but not all-cause (1.04; 0.91-1.18) or respiratory (1.13; 0.79-1.64) mortality than group B0. The exacerbation rate for group B1 was 0.6 events per patient-year versus 0.2 for group B0 (rate ratio, 2.55; 95% CI, 2.36-2.76). Results were similar for group A1 versus group A0. Conclusions: Stratification of GOLD A and B patients with one or no exacerbation in the past year provides valuable information on future risk, which should influence treatment recommendations for preventive strategies.

Interaction of smoking and social status on the risk of respiratory outcomes in a Swedish adult population: A Nordic Epilung study.

BACKGROUND: Evidence abounds on the independent roles of social class and smoking in relation to obstructive airway diseases, but data are sparse on the impact of their interaction. We evaluated whether and to what extent social class and smoking interact in relation to risk of respiratory diseases in adults. METHODS: Data from the population-based studies, West Sweden Asthma Study (WSAS, n = 23,753) and Obstructive Lung Disease in Northern Sweden studies (OLIN, n = 6519), were used, constituting randomly selected adults aged 20-75 years. Bayesian network analysis was used to estimate the probability for the interaction between smoking and socioeconomic status in relation to respiratory outcomes. RESULTS: Occupational and educational SES modified the association between smoking and the probability of allergic and non-allergic asthma. Former smokers who were at intermediate non manual employees and manual workers in service had higher probability of allergic asthma compared to professionals and executives. Furthermore, former smokers with primary education had higher probability of non-allergic asthma than those with secondary and tertiary education. Similarly, former smokers among professionals and executives had higher probability of non-allergic asthma than manual and home workers and primary educated. Likewise, allergic asthma due to former smoking was higher among highly educated compared to low educated. CONCLUSIONS: Beyond their independent roles, socioeconomic status and smoking interact in defining the risk of respiratory diseases. Clearer understanding of this interaction can help to identify population subgroups at most need of public health interventions.

Adjusted incidence, remission, and relapse of self-reported physician-diagnosed asthma and asthma medication usage in endurance athletes.

Longitudinal studies are needed to increase our knowledge of the natural history of asthma in athletes. Our aims were to estimate the incidence, remission, and relapse, of self-reported asthma among endurance athletes. A postal questionnaire on self-reported physician-diagnosed asthma, asthma medication, allergy, and respiratory symptoms was sent annually 2011-2015 to 666 Swedish elite athletes competing in cross-country skiing, biathlon, ski orienteering, or orienteering. Athletes at risk for (1) incident asthma were those without previous self-reported asthma, use of asthma medication, or asthma-like symptoms, (2) remission those who discontinued asthma medication usage and (3) relapse those who resumed asthma medication usage during the observation period. The population at risk was used as denominator in the calculations of subsequent event rate. At baseline, 89% responded, the median age was 17 years and 47% were females. Of the 373 athletes with never asthma nor use of asthma medication/asthma-like symptoms at baseline, 31 (8%) reported physician-diagnosed asthma during follow-up, giving an adjusted incidence rate of asthma of 42/1000 person years. Among the 110 athletes with self-reported asthma and use of asthma medication at baseline, 26 (24%) discontinued use of asthma medication during the follow-up, giving a remission rate of 142/1000 person years. Of the 31 athletes with previous asthma and no use of asthma medication at baseline, 9 (29%) resumed use of asthma medication during follow-up, giving a relapse rate was 148/1000 person years. Elite endurance athletes have a high incidence of self-reported physician-diagnosed asthma. The remission and relapse of self-reported asthma medication usage in endurance athletes appear similar to that of the general population.

Socioeconomic inequalities in asthma and respiratory symptoms in a high-income country: changes from 1996 to 2016.

Objective: Low socioeconomic status based both on educational level and income has been associated with asthma and respiratory symptoms, but changes over time in these associations have rarely been studied. The aim was to study the associations between educational or income inequality and asthma and respiratory symptoms among women and men over a 20-year period in northern Sweden. Methods: The study was performed within the Obstructive Lung disease in Northern Sweden (OLIN) research program. Mailed questionnaire surveys were administered to a random sample of adults (20-69 years of age) living in Sweden, in 1996, 2006 and 2016. Data on educational level and income were collected from the national integrated database for labor market research. Results: The educational inequality associated with asthma and asthmatic wheeze tended to decrease from 1996 to 2016, while it increased for productive cough, the latter among men not among women. The income inequality decreased for productive cough, especially for women, while no clear overall trends were found for asthmatic wheeze and asthma, apart from a decrease in income inequality regarding asthma among men. Conclusion: The patterns for socioeconomic inequality differed for asthma and wheeze compared to productive cough, and the results emphasize that education and income do not mirror the same aspects of socioeconomic inequality in a high-income country. Our findings are important for decision makers, not the least on a political level, as reduced inequality, e.g. through education, could lead to reduced morbidity.

Peripapillary Vessel Density in Relation to Optic Disc Drusen: A Multimodal Optical Coherence Tomography Study.

BACKGROUND: Optic disc drusen (ODD) are acellular calcified deposits within the optic nerve head known to cause visual field defects. An emerging gold standard for the diagnosis of ODD is enhanced depth imaging optical coherence tomography (EDI-OCT). The presence of ODD affects the adjacent peripapillary vasculature, which can be visualized using OCT angiography (OCTA). This study investigates the association between peripapillary vessel density and anatomical ODD location and volume using a newly developed method of multimodal OCT. METHODS: A case-control study with 16 patients diagnosed with ODD in the period 2008-2017 and 24 healthy controls. All patients and controls had EDI-OCT, OCTA, and demographic data collected. Using EDI-OCT and the medical imaging segmentation tool ITK-SNAP, 3-dimensional (3D) visualization of ODD in patients were created. ODD 3D visualization and corresponding OCTA scans were superimposed, making it possible to correlate ODD volume to the peripapillary vessel density in the corresponding modified Garway-Heath segments of the optic disc. RESULTS: We found that mean peripapillary vessel density across all modified Garway-Heath segments were lower in ODD patients compared with controls with significant reduction of peripapillary vessel density in the superior segment ( P = 0.03) and globally ( P = 0.05). A significant inverse proportionality between ODD volume and peripapillary vessel density in the corresponding segment was seen ( P = 0.002). CONCLUSIONS: We found a reduced peripapillary vessel density in regions with close anatomical proximity to ODD and inverse proportionality between ODD volume and peripapillary vessel density.