Diagnostic Potential of Oscillometry: A Population-based Approach.

Rationale: Respiratory resistance (Rrs) and reactance (Xrs) as measured by oscillometry and their intrabreath changes have emerged as sensitive parameters for detecting early pathological impairments during tidal breathing. Objectives: This study evaluates the prevalence and association of abnormal oscillometry parameters with respiratory symptoms and respiratory diseases in a general adult population. Methods: A total of 7,560 subjects in the Austrian LEAD (Lung, hEart, sociAl, boDy) Study with oscillometry measurements (computed with the Resmon Pro FULL; Restech Srl) were included in this study. The presence of respiratory symptoms and doctor-diagnosed respiratory diseases was assessed using an interview-based questionnaire. Rrs and Xrs at 5 Hz, their inspiratory and expiratory components, the area above the Xrs curve, and the presence of tidal expiratory flow limitation were analyzed. Normality ranges for oscillometry parameters were defined. Measurements and Main Results: The overall prevalence of abnormal oscillometry parameters was 20%. The incidence of abnormal oscillometry increased in the presence of symptoms or diagnoses: 17% (16-18%) versus 27% (25-29%), P < 0.0001. All abnormal oscillometry parameters except Rrs at 5 Hz were significantly associated with respiratory symptoms/diseases. Significant associations were found, even in subjects with normal spirometry, with abnormal oscillometry incidence rates increasing by 6% (4-8%; P < 0.0001) in subjects with symptoms or diagnoses. Conclusions: Abnormal oscillometry parameters are present in one-fifth of this adult population and are significantly associated with respiratory symptoms and disease. Our findings underscore the potential of oscillometry as a tool for detecting and evaluating respiratory impairments, even in individuals with normal spirometry.

Updated reference values for static lung volumes from a healthy population in Austria.

BACKGROUND: Reference values for lung volumes are necessary to identify and diagnose restrictive lung diseases and hyperinflation, but the values have to be validated in the relevant population. Our aim was to investigate the Global Lung Function Initiative (GLI) reference equations in a representative healthy Austrian population and create population-derived reference equations if poor fit was observed. METHODS: We analysed spirometry and body plethysmography data from 5371 respiratory healthy subjects (6-80 years) from the Austrian LEAD Study. Fit with the GLI equations was examined using z-scores and distributions within the limits of normality. LEAD reference equations were then created using the LMS method and the generalized additive model of location shape and scale package according to GLI models. RESULTS: Good fit, defined as mean z-scores between + 0.5 and -0.5,was not observed for the GLI static lung volume equations, with mean z-scores > 0.5 for residual volume (RV), RV/TLC (total lung capacity) and TLC in both sexes, and for expiratory reserve volume (ERV) and inspiratory capacity in females. Distribution within the limits of normality were shifted to the upper limit except for ERV. Population-derived reference equations from the LEAD cohort showed superior fit for lung volumes and provided reproducible results. CONCLUSION: GLI lung volume reference equations demonstrated a poor fit for our cohort, especially in females. Therefore a new set of Austrian reference equations for static lung volumes was developed, that can be applied to both children and adults (6-80 years of age).

Reference Equations for Within-Breath Respiratory Oscillometry in White Adults.

BACKGROUND: Within-breath analysis of oscillometry parameters is a growing research area since it increases sensitivity and specificity to respiratory pathologies and conditions. However, reference equations for these parameters in White adults are lacking and devices using multiple sinusoids or pseudorandom forcing stimuli have been underrepresented in previous studies deriving reference equations. The current study aimed to establish reference ranges for oscillometry parameters, including also the within-breath ones in White adults using multi-sinusoidal oscillations. METHODS: White adults with normal spirometry, BMI ≤30 kg/m2, without a smoking history, respiratory symptoms, pulmonary or cardiac disease, neurological or neuromuscular disorders, and respiratory tract infections in the previous 4 weeks were eligible for the study. Study subjects underwent oscillometry (multifrequency waveform at 5-11-19 Hz, Resmon PRO FULL, RESTECH Srl, Italy) in 5 centers in Europe and the USA according to international standards. The within-breath and total resistance (R) and reactance (X), the resonance frequency, the area under the X curve, the frequency dependence of R (R5-19), and within-breath changes of X (ΔX) were submitted to lambda-mu-sigma models for deriving reference equations. For each output parameter, an AIC-based stepwise input variable selection procedure was applied. RESULTS: A total of 144 subjects (age 20.8-86.3 years; height 146-193 cm; BMI 17.42-29.98 kg/m2; 56% females) were included. We derived reference equations for 29 oscillatory parameters. Predicted values for inspiratory and expiratory parameters were similar, while differences were observed for their limits of normality. CONCLUSIONS: We derived reference equations with narrow confidence intervals for within-breath and whole-breath oscillatory parameters for White adults.

Supranormal lung function: Prevalence, associated factors and clinical manifestations across the lifespan.

BACKGROUND AND OBJECTIVE: It is now well established that there are different life-long lung function trajectories in the general population, and that some are associated with better or worse health outcomes. Yet, the prevalence, clinical characteristics and risk factors of individuals with supranormal FEV1 or FVC values (above the upper-limit of normal [ULN]) in different age-bins through the lifetime in the general population are poorly understood. METHOD: To address these questions, we investigated the prevalence of supranormal FEV1 and FVC values in the LEAD (Lung, hEart, sociAl and boDy) study, a general population cohort in Austria that includes participants from 6 to 82 years of age. RESULTS: We found that: (1) the prevalence of supranormal pre-bronchodilator FEV1 and FVC values was 3.4% and 3.1%, respectively, and that these figures remained relatively stable through different age-bins except for participants >60 years., in whom they increased (5.0% and 4.2%, respectively). Approximately 50% of supranormal individuals had both increased FEV1 and FVC values; (2) supranormal spirometric values were consistently accompanied by higher static lung volumes and lower specific airway resistance through the lifespan, indicating better overall lung function; and (3) multivariate regression analysis identified that female sex, higher muscle mass (FFMI), less diabetes and fewer respiratory symptoms were consistently associated with supranormal FEV1 and FVC values. CONCLUSION: Supranormal FEV1 and/or FVC values occur in about 3% of the general population in different age bins and are associated with better health markers.

Blood eosinophil count in the general population: typical values and potential confounders.

There is growing interest in blood eosinophil counts in the management of chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). Despite this, typical blood eosinophil levels in the general population, and the impact of potential confounders on these levels have not been clearly defined.We measured blood eosinophil counts in a random sample of 11 042 subjects recruited from the general population in Austria. We then: 1) identified factors associated with high blood eosinophil counts (>75th percentile); and 2) excluded subjects with these factors to estimate median blood eosinophil counts in a "healthy" sub-population (n=3641).We found that: 1) in the entire cohort, age ≤18 years (OR 2.41), asthma (OR 2.05), current smoking (OR 1.72), positive skin prick test (OR 1.64), COPD (OR 1.56), metabolic syndrome (OR 1.41), male sex (OR 1.36) and obesity (OR 1.16) were significantly (p<0.05) associated with high blood eosinophil counts (binary multivariable logistic regression analysis), and had an additive effect; and 2) after excluding these factors, in those older than 18 years, blood eosinophil counts were higher in males than in females (median 120 (5%-95% CI: 30-330) versus 100 (30-310) cells·µL-1, respectively) and did not change with age.Median blood eosinophil counts in adults are considerably lower than those currently regarded as normal, do not change with age beyond puberty, but are significantly influenced by a variety of factors which have an additive effect. These observations will contribute to the interpretation of blood eosinophil levels in clinical practice.

Side-by-Side Comparison of Three Fully Automated SARS-CoV-2 Antibody Assays with a Focus on Specificity.

BACKGROUND: In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies rapidly have become available. However, the clinical performance of many of these is still insufficiently described. Therefore, we compared 3 commercial CE-marked, SARS-CoV-2 antibody assays side by side. METHODS: We included a total of 1154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients (≥14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. RESULTS: All 3 assays presented with high specificities: 99.2% (98.6-99.7) for Abbott, 99.7% (99.2-100.0) for Roche, and 98.3% (97.3-98.9) for DiaSorin. In contrast to the manufacturers' specifications, sensitivities only ranged from 83.1% to 89.2%. Although the 3 methods were in good agreement (Cohen's Kappa 0.71-0.87), McNemar tests revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictive values at 1% seroprevalence: 52.3% (36.2-67.9), 77.6% (52.8-91.5), and 32.6% (23.6-43.1) for Abbott, Roche, and DiaSorin, respectively. CONCLUSION: We found diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictive values of these tests.

Marked differences in prediabetes- and diabetes-associated comorbidities between men and women-Epidemiological results from a general population-based cohort aged 6-80 years-The LEAD (Lung, hEart, sociAl, boDy) study.

BACKGROUND: Based on biological and behavioural diversity sex and gender may affect comorbidities associated with prediabetes and diabetes. Besides evaluating the prevalence of prediabetes and diabetes (using fasting plasma glucose and HbA1c levels), the primary aim of the study is to investigate sex and gender differences in the prevalence of comorbidities in subjects with prediabetes and diabetes and to identify possible risk factors associated with prediabetes and diabetes. DESIGN: This observational, population-based cohort study included 11.014 subjects aged 6-80 years. Examinations included blood samples, ankle-brachial index, ECG, dual-energy X-ray absorptiometry scan and an interviewer-administered questionnaire. RESULTS: Across all ages, prevalence of prediabetes was 20.2% (male 23.6%; female 17.1%), and 5.4% for diabetes (male 7.3%; female 3.7%). The prevalence of prediabetes ranged from 4.4% (6-<10 years) up to 40.4% (70+ years) in men and from 4.8% up to 42.3% in women. Comorbidity profile was markedly different between male and female, particularly in those with prediabetes: women more often suffered from arrhythmia, noncoronary artery disease, osteoporosis, increased systemic inflammatory biomarkers and depression, while men with prediabetes more often showed angina pectoris, myocardial infarction and media sclerosis. CONCLUSIONS: The unexpected 4.6% prevalence of prediabetes in children aged 6-10 underscores the need for population-based studies across all ages and the onset of prevention of diabetes at a young age. Marked differences have been found in comorbidities as men with prediabetes and diabetes more often suffer from cardiovascular disease, while women more often show arrhythmia, noncoronary artery disease, increased systemic inflammatory biomarkers and depression.

The LEAD (Lung, Heart, Social, Body) Study: Objectives, Methodology, and External Validity of the Population-Based Cohort Study.

BACKGROUND: The Lung, hEart, sociAl, boDy (LEAD) Study (ClinicalTrials.gov; NCT01727518; http://clinicaltrials.gov) is a longitudinal, observational, population-based Austrian cohort that aims to investigate the relationship between genetic, environmental, social, developmental and ageing factors influencing respiratory health and comorbidities through life. The general working hypothesis of LEAD is the interaction of these genetic, environmental and socioeconomic factors influences lung development and ageing, the risk of occurrence of several non-communicable diseases (respiratory, cardiovascular, metabolic and neurologic), as well as their phenotypic (ie, clinical) presentation. METHODS: LEAD invited from 2011-2016 a random sample (stratified by age, gender, residential area) of Vienna inhabitants (urban cohort) and all the inhabitants of six villages from Lower Austria (rural cohort). Participants will be followed-up every four years. A number of investigations and measurements were obtained in each of the four domains of the study (Lung, hEart, sociAl, boDy) including data to screen for lung, cardiovascular and metabolic diseases, osteoporosis, and cognitive function. Blood and urine samples are stored in a biobank for future investigations. RESULTS: A total of 11.423 males (47.6%) and females (52.4%), aged 6-80 years have been included in the cohort. Compared to governmental statistics, the external validity of LEAD with respect to age, gender, citizenship, and smoking status was high. CONCLUSIONS: In conclusion, the LEAD cohort has been established following high quality standards; it is representative of the Austrian population and offers a platform to understand lung development and ageing as a key mechanism of human health both in early and late adulthood.

Associations of long-term exposure to air pollution and noise with body composition in children and adults: Results from the LEAD general population study.

BACKGROUND: While long-term air pollution and noise exposure has been linked to increasing cardiometabolic disease risk, potential effects on body composition remains unclear. This study aimed to investigate the associations of long-term air pollution, noise and body composition. METHODS: We used repeated data from the LEAD (Lung, hEart, sociAl, boDy) study conducted in Vienna, Austria. Body mass index (BMI; kg/m2), fat mass index (FMI; z-score), and lean mass index (LMI; z-score) were measured using dual-energy x-ray absorptiometry at the first (t0; 2011-ongoing) and second (t1; 2017-ongoing) examinations. Annual particulate matter (PM10) and nitrogen dioxide (NO2) concentrations were estimated with the GRAMM/GRAL model (2015-2021). Day-evening-night (Lden) and night-time (Lnight) noise levels from transportation were modeled for 2017 following the European Union Directive 2002/49/EC. Exposures were assigned to residential addresses. We performed analyses separately in children/adolescents and adults, using linear mixed-effects models with random participant intercepts and linear regression models for cross-sectional and longitudinal associations, respectively. Models were adjusted for co-exposure, lifestyle and sociodemographics. RESULTS: A total of 19,202 observations (nt0 = 12,717, nt1 = 6,485) from participants aged 6-86 years (mean age at t0 = 41.0 years; 52.9 % female; mean PM10 = 21 µg/m3; mean follow-up time = 4.1 years) were analyzed. Among children and adolescents (age ≤ 18 years at first visit), higher PM10exposure was cross-sectionally associated with higher FMI z-scores (0.09 [95 % Confidence Interval (CI): 0.03, 0.16]) and lower LMI z-scores (-0.05 [95 % CI: -0.10, -0.002]) per 1.8 µg/m3. Adults showed similar trends in cross-sectional associations as children, though not reaching statistical significance. We observed no associations for noise exposures. Longitudinal analyses on body composition changes over time yielded positive associations for PM10, but not for other exposures. CONCLUSION: Air pollution exposure, mainly PM10, was cross-sectionally and longitudinally associated with body composition in children/adolescents and adults. Railway/road-traffic noise exposures showed no associations in both cross-sectional and longitudinal analyses.

A Multivariant Surrogate Virus Neutralization Test Demonstrates Distinct SARS-CoV-2-Specific Antibody Responses in People Living with HIV after a Fourth Monovalent mRNA Vaccination or an Omicron Breakthrough Infection.

While neutralizing antibodies (nAbs) induced by monovalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations are primarily directed against the wildtype (WT), subsequent exposure to the Omicron variants may increase the breadth of the antibodies' cross-neutralizing activity. Here, we analyzed the impact of an Omicron breakthrough infection (BTI) or a fourth monovalent mRNA vaccination on nAb profiles in people living with human immunodeficiency virus (PLWH). Using a multivariant surrogate virus neutralization test (sVNT), we quantified nAbs in 36 three-times vaccinated PLWH, of whom 9 acquired a serologically confirmed Omicron BTI, 8 received a fourth vaccine dose, and 19 were neither infected nor additionally vaccinated. While nAbs against WT and Delta increased after the BTI and a fourth vaccination, a significant increase against BA.1, BA.2, and BA.5 was only observed after the BTI. However, there was no significant difference in nAb concentrations between the samples obtained after the BTI and fourth vaccination. In contrast, nAb levels were significantly lower in PLWH, who were neither infected nor additionally vaccinated after three vaccinations. Thus, our study demonstrates the suitability of a multivariant sVNT to assess hybrid humoral immunity after Omicron BTIs in PLWH vaccinated against SARS-CoV-2.

The effect of body compartments on lung function in childhood and adolescence.

BACKGROUND: There is an association between body composition and lung function, assessed by spirometry, but the effects of body compartments on static lung volumes and its changes during lung growth remain to be explored. We aimed to investigate the association of appendicular lean mass, reflecting skeletal muscle mass, and fat mass on forced and static lung function measures in childhood and adolescence. METHODS: In total, 1489 children and adolescents (6-18 years) of the observational, longitudinal (first and second visit within 4 years), general population-based LEAD study have been investigated. The association of appendicular lean mass and fat mass indices (ALMI and FMI; assessed by dual-energy X-ray absorptiometry) on lung function by spirometry (FEV1, FVC) and body plethysmography (TLC, RV, FRC) was investigated cross-sectionally. Longitudinal associations between lung function and body compartment changes between the two visits were analyzed. FINDINGS: The ALMI is positively associated with FEV1, FVC, and TLC. Contrary, FMI is inversely associated with lung function measures including FRC and RV. During the phase of lung growth, higher gain in muscle mass is associated with higher increases of FVC and TLC. INTERPRETATION: This study demonstrates the different effects of muscle and fat mass on forced expiratory and static lung volumes. Achieving and maintaining muscle mass in childhood and adolescence might become an important preventive strategy for lung health in adulthood.

Association of Preserved Ratio Impaired Spirometry (PRISm) with Arterial Stiffness.

RATIONALE: Preserved ratio impaired spirometry (PRISm) is a recently recognized spirometric pattern defined by forced expiratory volume in 1 second (FEV1) / Forced vital capacity ratio ≥0.70 and FEV1 <80% of reference. For unclear reasons, PRISm is associated with increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is a major mechanism of CV disease, which can be measured by carotid-femoral pulse wave velocity (cfPWV). OBJECTIVES: We explored the hypothesis that cfPWV would be increased in individuals with PRISm and airflow limitation (AL). METHODS: We measured forced spirometry, lung volumes by body plethysmography, and cfPWV in 9,466 subjects recruited from the general population in the Austrian cross-sectional LEAD study, and tested the association of arterial stiffness with PRISm and AL by multivariable linear regression analysis. Individuals aged 18 years and under as well as those with missing cfPWV or co-variates were excluded from further analysis. RESULTS: Individuals with PRISm (n = 431, 4.6%) were of similar age to those with normal spirometry (n = 8136, 85.9%) and significantly younger than those with AL (n = 899, 9.5%). Arterial hypertension, diabetes mellitus, coronary artery disease, heart failure and peripheral arterial occlusive disease were significantly more common in individuals with PRISm compared to normal lung function and similar to those with AL. There was a significant association between PRISm and arterial stiffness on bivariate linear regression analysis (crude model; ß = 0.038; 95% CI, 0.016 - 0.058), which persisted after robust adjustment for clinical confounders upon multivariable analysis (final model; ß = 0.017; 95% CI, 0.001 - 0.032). CfPWV was significantly higher in individuals with PRISm irrespective of the presence of established CV disease or pulmonary restriction. AL also showed a significant association with arterial stiffness on multivariable linear regression analysis (final model; 95% CI, ß = 0.025, 0.009 - 0.042). CONCLUSIONS: Arterial stiffness measured by cfPWV is increased in individuals with PRISm independent from CV disease and risk factors. The pathobiological mechanisms underlying this association deserve further research.

Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study.

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

Prevalence of restrictive lung function in children and adults in the general population.

BACKGROUND: Restrictive lung function (RLF) is characterized by a reduced lung expansion and size. In the absence of lung volume measurements, restriction can be indirectly assessed with restrictive spirometric patterns (RSP) by spirometry. Prevalence data on RLF by the golden standard body plethysmography in the general population are scarce. Therefore, we aimed to evaluate the prevalence of RLF and RSP in the general population by body plethysmography and to determine factors influencing RLF and RSP. METHODS: Pre-bronchodilation lung function data of 8891 subjects (48.0% male, age 6-82 years) have been collected in the LEAD Study, a single-centered, longitudinal, population-based study from Vienna, Austria. The cohort was categorized in the following groups based on the Global Lung Initiative reference equations: normal subjects, RLF (TLC < lower limit of normal (LLN)), RSP (FEV1/FVC ≥ LLN and a FVC < LLN), RSP only (RSP with TLC ≥ LLN). Normal subjects were considered those with FEV1, FVC, FEV1/FVC and TLC between LLN and ULN (upper limit of normal). RESULTS: The prevalence of RLF and RSP in the Austrian general population is 1.1% and 4.4%. Spirometry has a positive and negative predictive value of 18.0% and 99.6% to predict a restrictive lung function. Central obesity was associated with RLF. RSP was related to smoking and underweight. CONCLUSIONS: The prevalence of true restrictive lung function and RSP in the Austrian general population is lower than previously estimated. Our data confirm the need for direct lung volume measurement to diagnose true restrictive lung function.

Asthma Prevalence and Phenotyping in the General Population: The LEAD (Lung, hEart, sociAl, boDy) Study.

Background: Asthma is a chronic heterogeneous respiratory disease involving differential pathophysiological pathways and consequently distinct asthma phenotypes. Objective and Methods: In the LEAD Study, a general population cohort (n=11.423) in Vienna ranging from 6-82 years of age, we addressed the prevalence of asthma and explored inflammatory asthma phenotypes that included allergic and non-allergic asthma, and within these phenotypes, an eosinophilic (eosinophils ≥300 cells/µL, or ≥150 cells/µL in the presence of ICS medication) or non-eosinophilic (eosinophils <300 cells/µL, or <150 cells/µL in the presence of ICS) phenotype. In addition, we compared various factors related to biomarkers, body composition, lung function, and symptoms in control subjects versus subjects with current asthma (current doctor's diagnosis of asthma). Results: An overall prevalence of 4.6% was observed for current asthma. Furthermore, an age-dependent shift from allergic to non-allergic asthma was found. The non-eosinophilic phenotype was more prominent. Obesity was a prevalent condition, and body composition including visceral adipose tissue (VAT), is affected in current asthma versus controls. Conclusion: This broad-aged and large general population cohort identified differential patterns of inflammatory asthma phenotypes that were age-dependent. The presence of eosinophilia was associated with worse asthma control, increased asthma medication, increased VAT, and lower lung function, the opposite was found for the presence of an allergic asthma.

Prevalence of dyspnea in general adult populations: A systematic review and meta-analysis.

INTRODUCTION: Dyspnea is a commonly described symptom in various chronic and acute conditions. Despite its frequency, relatively little is known about the prevalence and assessment of dyspnea in general populations. The aims of this review were: 1) to estimate the prevalence of dyspnea in general adult populations; 2) to identify associated factors; and 3) to identify used methods for dyspnea assessment. METHODS: A systematic literature search was conducted using MEDLINE/PubMed, Embase, CINAHL and JAMA network. Records were screened by two independent reviewers and quality was assessed by using the Joanna Briggs Institute checklist for risk of bias in prevalence studies. Multi-level meta-analysis was performed to estimate pooled prevalence. The protocol was registered on PROSPERO (CRD42021275499). RESULTS: Twenty original articles, all from studies in high-income countries, met the criteria for inclusion. Overall, their quality was good. Pooled prevalence of dyspnea in general adult populations based on 11 studies was 10% (95% CI 7, 15), but heterogeneity across studies was high. The most frequently reported risk factors were increasing age, female sex, higher BMI and respiratory or cardiac disease. The MRC or the modified MRC scale was the most used tool to assess dyspnea in general populations. CONCLUSIONS: Dyspnea is a common symptom in adults in high-income countries. However, the high heterogeneity across studies and the lack of data from low- and middle-income countries limit the generalizability of our findings. Therefore, more research is needed to unveil the prevalence of dyspnea and its main risk factors in general populations around the world.