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OBJECTIVES: Patients with severe primary mitral regurgitation (PMR) remain asymptomatic at first. In the long term, however, severe PMR leads to cardiac decompensation. Exercise testing in asymptomatic PMR is recommended in selected patients by guidelines. Cardiopulmonary exercise testing (CPET), which additionally measures ventilation (VE), oxygen consumption (VO₂) and carbon dioxide production (VCO₂), has been scarcely studied in PMR. We hypothesized that CPET might have prognostic value in asymptomatic PMR and therefore studied if CPET, including assessment of ventilation efficiency, has prognostic value for asymptomatic patients with severe PMR.

METHODS: Asymptomatic patients with severe PMR were prospectively recruited between 2013 and 2018. Exclusion criteria were coronary artery disease, chronic kidney disease, diabetes mellitus, concomitant valve disease, symptomatic lung disease or class 1 recommendation for valvular surgery. Echocardiography and serial CPET were conducted at one university hospital in Sweden. Primary outcome was mitral valve intervention.

RESULTS: Forty-eight patients were recruited to the study. Median follow-up period was 4.4 (2.1-6.9) years, during which 28 (58%) patients underwent mitral valve surgery. Ventilation efficiency, the relationship of VE to VCO₂ during CPET, predicted surgical treatment of the mitral valve. Increased VE/VCO₂ ratio at the anaerobic threshold had the highest predictive value, remaining an independent predictor after adjusting for impaired VO₂ at peak exercise (HR 4.42 (1.52-12.92), p = 0.007) and echocardiographic thresholds for left ventricular and atrial remodelling, as defined by current guideline-based recommendation for intervention (HR 3.72 (1.41-9.82), p = 0.008).

CONCLUSION: Impaired ventilatory efficiency, but not peak VO₂, predicted surgical treatment of the mitral valve in asymptomatic patients with severe PMR. Ventilatory efficiency, a CPET index less dependent on peak exercise performance, may be a new useful tool in risk stratification.

BACKGROUND: Air pollution and greenness impact respiratory health, but intergenerational effects remain unclear.We investigated whether pre-conception parental residential exposure to air pollution and greenness at age 20-44 years is associated with offspring asthma outcomes in the Lifespan and inter-generational respiratory effects of exposures to greenness and air pollution (Life-GAP) project.

METHODS: We analyzed data on 3684 RHINESSA study participants born after the year 1990 (mean age 19, standard deviation 4), offspring of 2689 RHINE study participants. Modelled annual concentrations of particulate matter (PM_2.5, PM₁₀), nitrogen dioxide (NO₂), elemental carbon (EC), and ozone (O₃), and greenness (Normalized Difference Vegetation Index, NDVI) were assigned to parental residential addresses in 1990, corresponding to 1-18 years prior to birth (mean: 6 years, SD: 5). We analyzed associations using generalized structural equation modelling (GSEM), with cluster-robust standard errors allowing for intra-family correlation, while adjusting for potential confounders.

RESULTS: Among offspring participants, 18% reported lifetime asthma, 9% active asthma, 8% asthma medication, 5% asthma attacks, and 37% any asthma symptom. An interquartile range (IQR) increase in parental residential NDVI exposure was associated with less lifetime asthma (OR = 0.79, 95%CI: 0.64, 0.98 per 0.3 units). Similar associations were observed for active asthma and asthma medication use. Associations of air pollution with asthma outcomes were inconclusive.

CONCLUSION: Parental exposure to residential green spaces before conception was associated with lower asthma risk in offspring. Urban planning policies prioritizing green spaces may be a key public health intervention for future cities.

INTRODUCTION: Asthma may increase the risk of comorbidities and systemic inflammation, but population data are scarce. This study aimed to compare comorbidities and systemic inflammation between those with and without current asthma and to identify characteristics linked to comorbidities and biomarkers.

METHODS: In a cross-sectional analysis of 28 828 people aged 50-64 in the Swedish CArdioPulmonary bioImage Study, assessments included postbronchodilator forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), serum levels of C reactive protein (CRP) and haemoglobin A1c (HbA1c). Data on current physician-diagnosed asthma, respiratory symptoms and comorbidities were obtained via a questionnaire.

RESULTS: The prevalence of current asthma was 6.3%. Current asthma was independently associated with a higher prevalence of hypertension (OR=1.30; 95% CI 1.16 to 1.46), hyperlipidaemia (OR=1.20; 95% CI 1.04 to 1.39), diabetes (OR=1.42; 95% CI 1.16 to 1.75), coeliac disease (OR=2.52; 95% CI 1.61 to 3.95) and rheumatic disease (OR=1.43; 95% CI 1.16 to 1.78). Asthma was also associated with higher levels of CRP (beta=0.25; 95% CI 0.06 to 0.44) and HbA1c (beta=0.47; 95% CI 0.18 to 0.77). In those with asthma, lower FVC % predicted was associated with a higher likelihood of hypertension (OR=1.10; 95% CI 1.01 to 1.19), diabetes (OR=1.47; 95% CI 1.26 to 1.71) and rheumatic disease (OR=1.22; 95% CI 1.05 to 1.42). Lower FEV₁ % predicted was associated with a higher likelihood of diabetes (OR=1.27; 95% CI 1.12 to 1.44). FVC % and FEV₁ % predicted were negatively associated with CRP and HbA1c.

CONCLUSIONS: Our findings suggest that in middle-aged people, asthma is independently associated with common comorbidities such as hypertension, diabetes and rheumatic disease, as well as elevated CRP and blood glucose. Our data suggest that some associations are connected with lung function impairment in those with asthma.

Background: Bronchodilator responsiveness testing is mainly used for diagnosing asthma. We aimed to investigate whether it is associated with progression to chronic airflow obstruction over time.

Methods: The multinational Burden of Obstructive Lung Disease cohort study surveyed adults, aged 40 years and above, at baseline and followed them up after a mean of 9.1 years. Recruitment took place between January 2, 2003 and December 26, 2016. Follow-up measurements were collected between January 29, 2019 and October 24, 2021. On both occasions, study participants provided information on respiratory symptoms, health status and several environmental and lifestyle exposures. They also underwent pre- and post-bronchodilator spirometry. We defined bronchodilator responsiveness at baseline using the American Thoracic Society and European Respiratory Society (ATS/ERS) 2022 definition, and the presence of chronic airflow obstruction at follow-up as a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio (FEV₁/FVC) less than the lower limit of normal. We used multi-level regression models to estimate the association between baseline bronchodilator responsiveness and incident chronic airflow obstruction. We stratified analyses by gender and performed a sensitivity analysis in never smokers.

Findings: We analysed data from 3701 adults with 56% being women. Compared to those without bronchodilator responsiveness at baseline, those with bronchodilator responsiveness had 36% increased risk of developing chronic airflow obstruction (RR: 1.36, 95%CI 1.04, 1.80). This effect was stronger in women (RR: 1.45, 95%CI 1.09, 1.91) than men (RR: 1.07, 95%CI 0.51, 2.24). Never smokers with bronchodilator responsiveness also were at greater risk of incident chronic airflow obstruction (RR: 1.48, 95%CI 1.01, 2.20).

Interpretation: Bronchodilator responsiveness appears to be a risk factor for incident chronic airflow obstruction. It is important that future studies in other large population-based cohorts replicate these findings.

Systemic inflammation is important in many medical conditions. Activation markers of inflammatory cells can be quantified, but are less studied. Therefore, we studied individual characteristics and diseases in relation to neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO), both for neutrophils, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and mast cell tryptase. Spirometry and serum biomarkers were assessed in 498 participants (252 males) aged ≥ 40 years from the Uppsala center of the population-based Burden of Obstructive Lung Disease study. Higher MPO, NGAL and EDN levels related to heart disease. Higher ECP and EDN levels were both related to asthma while higher EDN related to male sex and atopy. Higher tryptase levels were found in subjects with obesity, chronic airflow limitation (CAL), or hypertension. In multivariate analyses, subjects with heart disease had 22.1% (95% confidence interval 4.1%, 43.3%) higher MPO, 19.3% (7.8%, 31.9%) higher NGAL, and 23.2% (3.0%, 47.3%) higher EDN than subjects without heart disease. The association between CAL and tryptase was not consistent after adjustment for age and BMI as continuous variables. The higher EDN levels in heart disease is a novel finding that require further studies to elucidate the clinical importance.

Purpose: Chronic rhinosinusitis (CRS) is related to asthma and chronic obstructive pulmonary disease (COPD). However, combined data on CRS, pulmonary function, lower airway symptoms, and cigarette smoking from the general population are lacking. The current study investigates the relationships between CRS and chronic airflow limitation (CAL), lower airway symptoms and COPD in a middle-aged population of ever-smokers and never-smokers.

Patients and Methods: All subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS) were included. Subjects underwent spirometry after bronchodilation. Chronic airflow limitation was defined as FEV₁/FVC ratio <0.7. Computed tomography imaging of the thorax was performed to detect the presence of emphysema, and the subjects answered a comprehensive questionnaire on CRS, lower airway symptoms, asthma, chronic bronchitis, and cigarette smoking habits.

Reslutls: In total, 30,154 adult subjects in the age range of 50-64 years were included. The prevalence of CRS was 5.6%. CRS was more-prevalent among subjects in the following categories: CAL (7.6%), lower airway symptoms (15.7%), current smokers (8.2%), asthma (13.6%), never-smokers and ever-smokers with COPD (17.6% and 15.3%, respectively), emphysema (6.7%), and chronic bronchitis (24.5%). In the adjusted regression model, CRS was significantly associated with CAL (OR 1.40), lower airway symptoms (OR 4.59), chronic bronchitis (OR 6.48), asthma (OR 3.08), and COPD (OR 3.10).

Conclusion: In this national, randomly chosen population sample of more than 30,000 middle-aged men and women, CRS is associated with CAL, lower airway symptoms, chronic bronchitis, asthma, and COPD. In patients with CRS and in patients with lower airway inflammation, it is important to consider the inflammatory status of the entire airway system.

Background: In 2017, Burgel and colleagues developed an algorithm to identify clinical phenotypes that predict mortality in COPD. Our study aimed to 1) investigate whether the phenotypes can predict acute exacerbations of COPD (AECOPD) and 2) validate their ability to predict mortality.

Methods: The Tools Identifying Exacerbations (TIE) cohort study recruited participants with spirometry-verified COPD from primary and secondary care in three Swedish regions. Participants were allocated to phenotypes 1–5 using the previously developed algorithm containing comorbidities (heart failure, coronary artery disease, hypertension, and/or diabetes), dyspnoea, age, forced expiratory volume in 1 s (FEV1), and body mass index (BMI). Data on AECOPDs and deaths during the three-year follow-up were collected from medical records and analysed with Cox proportional hazards regressions. Harrel's C-index was used to assess the models' discriminative ability.

Results: Among the 566 participants, 59 % were female, and the mean ± SD FEV1 was 57 ± 18 % of predicted. The hazard ratios (HRs) [95 % CI] for time to AECOPD were 3.04 [1.93–4.79], 2.38 [1.54–3.66], and 3.52 [1.73–7.15] in phenotypes 1, 2, and 4 compared with 5 (C-index = 0.61). When AECOPD history was used to predict future AECOPD the C-index was 0.65.The HRs [95 % CI] for mortality were 8.24 [1.93–35.3], 6.26 [1.40–28.0], and 16.7 [3.25–86.3] in phenotypes 1, 3, and 4 compared to 5 (C-index = 0.68). For AECOPD history, the C-index was 0.55.

Conclusion: Clinical COPD phenotypes based on comorbidities, dyspnoea, age, FEV1, and BMI predict AECOPDs but do not perform better than AECOPD history. However, they perform better than AECOPD history in predicting mortality.

Introduction We investigated whether the forced expiratory volume in 6 s (FEV6) can be used as a surrogate for the forced vital capacity (FVC).

Methods The Burden of Obstructive Lung Disease is a multinational cohort study. At baseline, data were collected from adults, aged 40 years or older, from 41 sites across 34 countries. Participants from 18 sites were followed-up after a median of 8.3 years. Participants who completed the study core questionnaire and had acceptable post-bronchodilator spirometry were included. We performed receiver operating characteristic analyses to measure the ability of FEV1/FEV6 less than the lower limit of normal (LLN) to correctly classify FEV1/FVC less than the LLN, and FEV6 less than the LLN to correctly classify FVC less than the LLN. We used multilevel regression analyses to assess the association of discordant measurements with respiratory symptoms, quality of life and lung function decline.

Results At baseline, 28 604 participants were included. 53% were female (15 060). 10% (2876) had chronic airflow obstruction for FEV1/FVC, compared with 9% (2704) for FEV1/FEV6. 37% (10 637) had spirometric restriction for FVC, compared with 35% (9978) for FEV6. The FEV1/FEV6 had excellent accuracy in identifying FEV1/FVC less than the LLN (area under the curve (AUC): 0.90, 95% CI, 0.89 to 0.91, kappa coefficient 0.82). The FEV6 also had excellent agreement in identifying FVC less than the LLN (AUC: 0.95, 95% CI, 0.94 to 0.95, kappa coefficient 0.90). Discordant reductions in FEV1/FEV6 (1%, 345) and FEV6 (1%, 309) were associated with greater odds of having respiratory symptoms and a lower physical quality of life. 3870 participants were followed up. Those with discordant reductions in FEV1/FEV6 and FEV6 were more likely to have chronic airflow obstruction and spirometric restriction at follow-up.

Conclusions There is strong agreement between the FVC and FEV6 in the identification of chronic airflow obstruction and spirometric restriction.

Background

Evidence suggest an inflammatory link between respiratory health and periodontitis. This study aims to evaluate the impact of periodontal therapy on lung function.

Methods

Sixty-two never-smoking patients with mild periodontitis and without other medical conditions participated in this single-blind, prospective trial. Patients underwent periodontal therapy following an infection control approach. Lung function was measured using forced oscillation technique, assessing airway resistance and reactance, and spirometry evaluating FEV₁, FVC, and FEV₁/FVC. Lung function and fractional exhaled nitric oxide were assessed at baseline, three and six weeks, and every three months for a year. Periodontal parameters were recorded at baseline, six weeks, six and 12 months. Data were analysed using mixed-effects regression models.

Results

Patients (mean age 36 years, 58% female) showed significant improvements in periodontal parameters (p < 0.001). Oscillometry revealed a significant decrease in airway resistance at 11 Hz and 19 Hz after six weeks, with further significant decreases throughout the study. Resistance at 5 Hz (R₅) consistently declined, reaching significance at three months (p = 0.001). By one year, R₅, R₁₁, R₁₉, and R_5 − 20 showed significant reductions (all p < 0.05). Airway reactance at 5 Hz became less negative at three months (p = 0.002), while the reactance area (AX) decreased significantly at six months (p = 0.008). No significant changes were observed in spirometry or fractional exhaled nitric oxide.

Conclusion

A decrease in airway resistance was observed after periodontal therapy, underscoring its positive impact on small airway function. These findings suggest that oral infection control is valuable for respiratory health in young adults before chronic conditions establish.

Clinical trial registration

The trial was registered at ClinicalTrials.gov (NCT04781153) on February 19, 2021, prior to participant enrolment.