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Background: Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. The aims of this study were to estimate the prevalence of dyspnoea across several world regions, and to investigate the association of dyspnoea with lung function.

Methods: Dyspnoea was assessed, and lung function measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥ 2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis.

Results: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC<LLN: OR 2.07, 95 %CI 1.75-2.45) and spirometry airflow obstruction (FEV₁/FVC<LLN: OR 3.76, 95 %CI 1.04-4.65). These associations did not significantly differ between sexes, age groups or smoking history. The association of dyspnoea with airflow obstruction was weaker among obese participants (OR 2.20, 95 %CI 1.61-3.01).

Conclusion: The prevalence of dyspnoea varies substantially across the world and is strongly associated with lung function impairment. Using the mMRC scale in epidemiological research should be discussed.

Background

Comorbid conditions and breathlessness are associated with poor outcomes in chronic obstructive pulmonary disease (COPD). We evaluated the associations of comorbid heart disease and depression/anxiety with breathlessness in daily life among people with COPD.

Methods

Cross-sectional analysis from the PRAXIS cohort in central Sweden. Data on patient characteristics and the modified Medical Research Council (mMRC) and Dyspnea-12 breathlessness instruments (D-12) were obtained from questionnaires in 2022. Lung function data were collected from record review. Outcome variables were clinically significant breathlessness defined as mMRC≥2 and D-12 total (>2.7), physical (>1.4) and affective (>1.2) scores above published minimal clinical important differences. Associations of heart disease and depression/anxiety with each outcome were analyzed using multivariable Poisson regression adjusted for relevant confounders.

Results

In 522 included patients, mMRC ≥2 was present in 59 % and increased D-12 total, physical and affective domain scores in 69 %, 74 %, and 50 %, respectively. Heart disease was independently associated with mMRC (relative risk ratio [95 % confidence interval] 1.34 [1.17–1.53]), D12 physical domain (1.12[1.02–1.24]) and D-12 affective domain (1.20[1.02–1.42]). Depression/anxiety was independently associated with increased D-12 affective domain (1.25[1.04–1.49]). In addition, previous exacerbations and GOLD stage 3–4 were associated with mMRC and D-12, respectively.

Conclusion

In COPD, comorbid heart disease is associated with both activity-related breathlessness and with physical and affective domains of breathlessness while depression/anxiety is associated with the affective domain of breathlessness. As the influence of different dimensions of breathlessness may differ according to comorbidity the D-12 instrument adds more information when assessing breathlessness in patients with COPD.

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.

BACKGROUND: Limited studies have investigated the influence of body mass index (BMI) trajectories on lung function covering the entire growth period.

METHODS: We conducted a prospective study utilizing data from the Swedish BAMSE birth cohort. Latent class mixture modelling was employed to examine the diversity in BMI z-scores from birth to 24 years of age. Participants with four or more BMI z-scores were included (n=3204, 78·4%). Pre-bronchodilator (BD) spirometry was tested at 8, 16, and 24 years, while post-BD spirometry, multiple-breath nitrogen washout (for lung clearance index, LCI), and urinary metabolomics data were assessed at 24 years.

RESULTS: Six distinct BMI development groups were identified. Compared to the stable normal BMI group, the accelerated increasing BMI group exhibited reduced pre- and post-BD FEV₁/FVC ratio z scores (β=-0·26, 95% CI=[-0·44, -0·08], and -0·22, [ -0·39, -0·05], respectively), along with elevated LCI (0·30, [0·22, 0·42]) at 24 years. The persistent high BMI group demonstrated lower FEV₁, and FVC z scores growth between 16 and 24 years (-0.24, [-0.42, -0.05], and -0.27, [-0.45, -0.01], respectively), and elevated LCI (0·20, [0·03, 0·39]) at 24 years. However, those impairments were not observed in the accelerated resolving BMI group. Conversely, the persistent low BMI group displayed persistently decreased FEV₁, and FVC from 8 to 24 years, as well as decreased lung function growth. Additionally, histidine-related metabolites were associated with pre- and post-BD FEV₁ (hypergeometric FDR=0.008 and <0.001, respectively).

CONCLUSIONS: Early interventions aiming for normal BMI during childhood may contribute to improved lung health later in life.

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.

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.

RESULTS: 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.

Spirometry is used to determine what is “unusual” lung function compared with what is “usual” for healthy non-smokers. This study aimed to investigate regional variation in the forced vital capacity (FVC) and in the forced expiratory volume in one second to FVC ratio (FEV₁/FVC) using cross-sectional data from all 41 sites of the multinational Burden of Obstructive Lung Disease study. Participants (5,368 men; 9,649 women), aged ≥40 years, had performed spirometry, had never smoked and reported no respiratory symptoms or diagnoses. To identify regions with similar FVC, we conducted a principal component analysis (PCA) on FVC with age, age² and height², separately for men and women. We regressed FVC against age, age² and height², and FEV₁/FVC against age and height², for each sex and site, stratified by region. Mean age was 54 years (both sexes), and mean height was 1.69 m (men) and 1.61 m (women). The PCA suggested four regions: 1) Europe and richer countries; 2) the Near East; 3) Africa; and 4) the Far East. For the FVC, there was little variation in the coefficients for age, or age², but considerable variation in the constant (men: 2.97 L in the Far East to 4.08 L in Europe; women: 2.44 L in the Far East to 3.24 L in Europe) and the coefficient for height². Regional differences in the constant and coefficients for FEV₁/FVC were minimal (<1%). The relation of FVC with age, sex and height varies across and within regions. The same is not true for the FEV₁/FVC ratio.

BACKGROUND: Low-grade systemic inflammation is linked to abnormal spirometry. Impulse oscillometry (IOS) is sensitive in detecting peripheral airway dysfunction, but inflammation in relation to IOS is poorly studied. The objectives of the present study were to analyse associations between C-reactive protein (CRP), blood eosinophils (B-Eos), blood neutrophils (B-Neu), blood lymphocytes (B-Lym), blood leukocytes (B-Leu), blood monocytes (B-Mono) and IOS.

METHODS: Blood biomarkers and IOS were assessed in 10 602 adults (aged 50-65 years) within the Swedish CardioPulmonary bioImage Study (SCAPIS). Upper tertiles for CRP (>1.80 mg·L^-1), B-Eos (>0.20 10⁹·L^-1), B-Neu (>3.40 10⁹·L^-1), B-Lym (>2.00 10⁹·L^-1), B-Leu (>6.10 10⁹·L^-1) and B-Mono (>0.50 10⁹·L^-1) were analysed in relation to the following abnormal IOS indices: resistance at 5 Hz, resistance at 20 Hz, area of reactance, resonant frequency (>95th percentile) and reactance at 5 Hz (<5th percentile), based on healthy, never-smoking SCAPIS participants.

RESULTS: Abnormal IOS was observed in 1715 (16.2%), of which 580 (33.8%) also had abnormal spirometry. Having several blood biomarkers in the upper tertile (1, 2-3 or 4-6 versus 0) was overall associated with abnormal IOS; adjusted odds ratios (OR) and 95% confidence intervals (CI) ranging from 1.19 (1.02-1.38) to 2.27 (1.79-2.89). Furthermore, having 2-3 or more blood biomarkers versus 0 in the upper tertile was overall linked to abnormal IOS in participants with normal spirometry; adjusted OR (95% CI) ranging from 1.43 (1.17-1.75) to 1.75 (1.29-2.38).

CONCLUSIONS: Low-grade systemic inflammation was related to abnormal IOS and appeared consistent even when participants had normal spirometry.