Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease:a cross-sectional analysis of ten population-based studies

Background: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. Methods: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09-0·14; p<0·0001). Interpretation: If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity. Funding: The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme

COPD Diagnosis: Time for Disruption

Articulating a satisfactory definition of a disease is surprisingly difficult. Despite the alarming individual, societal and economic burden of chronic obstructive pulmonary disease (COPD), diagnosis is still largely based on a physiologically dominated disease conception, with spirometrically determined airflow limitation as a cardinal feature of the disease. The diagnostic inaccuracy and insensitivity of this physiological disease definition is reviewed considering scientific developments of imaging of the respiratory system in particular. Disease must be approached as a fluid concept in response to new scientific and medical discoveries, but labelling as well as mislabelling someone as diseased, will have enormous individual, social and financial implications. Nosology of COPD urgently needs to dynamically integrate more sensitive diagnostic procedures to detect the breadth of abnormalities early in the disease process. Integration of broader information for the identification of abnormalities in the respiratory system is a cornerstone for research models of underlying pathomechanisms to create a breakthrough in research

Combined analysis of five non-interventional studies of the effectiveness, tolerability, and safety of the extrafine fixed dose beclomethasone/ formoterol combination in the treatment of asthma in Austria

Objective: The real-world effectiveness and tolerability of an extrafine fixed dose beclomethasone/formoterol (BDP/FF) treatment of patients with partially or non-controlled asthma was evaluated in five non-interventional studies (NISs) from Austria.Methods: Asthma patients enrolled in these five NISs were treated with beclomethasone/formoterol (Foster (R) or Foster (R) Nexthaler (R)) as maintenance and reliever over 12 weeks. Asthma control, lung function and symptom scores were assessed at baseline, after 4-8 weeks and at the end of the investigations in week 12. In addition, tolerability and handling of the devices were evaluated by questionnaires.Results: The combined analysis included 891 patients (53% female, aged 49.3 years) demonstrating significant improvements in asthma control, lung function parameters (PEF, FEV1 and FVC) and symptom scores (reduction of breathlessness, wheezing, chest tightness and cough). These changes were already detectable after 4-8 weeks. The treatment was effective irrespective of smoking status, exercise, or previous medication. Tolerability of the therapy with extrafine BDP/FF was rated as "very good" or "good" in 98% of the patients. 95% of the patients intended to continue the treatment, and nearly all (99%) rated the handling of the device as "very good" or "good". No serious adverse reactions were reported.Conclusions: This combined analysis of five non-interventional studies confirms the effectiveness and tolerability of the extrafine fixed-dose BDP/FF combination (Foster (R) and Foster (R) Nexthaler (R)) in a heterogenous patient population suffering from partially or non-controlled asthma. Therapy was associated with a high patient satisfaction and the absence of serious adverse reactions.Peer reviewe

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 conse-quently 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/mu L, or >150 cells/mu L in the presence of ICS medication) or non-eosinophilic (eosinophils <300 cells/mu L, or <150 cells/mu L 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

Using Body Composition Groups to Identify Children and Adolescents at Risk of Dyslipidemia

The impact of body composition on the early origin of chronic diseases is an increasingly appreciated phenomenon. Little is known about the characteristics of children with varying body composition. The aim of this study was to investigate serum lipid profiles and other characteristics in relation to body composition. The data of 1394 participants (aged 6 to &lt;18 years) of the observational general population-based Austrian LEAD Study have been analyzed. Body composition groups were defined by appendicular lean mass (ALMI) and fat mass (FMI) indices assessed by DXA. Serum lipid profiles (triglycerides, LDL-c, HDL-c) and other characteristics (e.g., prematurity, smoke exposure, physical activity, nutrition) were investigated in these body composition groups. Different body composition groups, which are not distinguishable by BMI, exist. Children with high ALMI and high FMI showed higher triglycerides and LDL-c, but lower HDL-c levels. In contrast, levels did not differ between those with high FMI but low (or normal) ALMI, and other body composition groups. BMI should be interpreted cautiously, and body composition should be measured by more precise techniques. In particular, children and adolescents with high FMI who have concomitantly high ALMI should be followed closely in future studies to investigate whether they are at increased risk of cardiovascular problems.ISSN:2227-906

Nordic Walking improves daily physical activities in COPD: a randomised controlled trial

ABSTRACT: BACKGROUND: In patients with COPD progressive dyspnoea leads to a sedentary lifestyle. To date, no studies exist investigating the effects of Nordic Walking in patients with COPD. Therefore, the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages. Furthermore we aimed to determine the short- and long-term effects of Nordic Walking on COPD patients' daily physical activity pattern as well as on patients exercise capacity. METHODS: Sixty COPD patients were randomised to either Nordic Walking or to a control group. Patients of the Nordic Walking group (n = 30; age: 62 +/- 9 years; FEV1: 48 +/- 19% predicted) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75% of their initial maximum heart rate three times per week, whereas controls had no exercise intervention. Primary endpoint: daily physical activities (measured by a validated tri-axial accelerometer); secondary endpoint: functional exercise capacity (measured by the six-minute walking distance; 6MWD). Assessment time points in both groups: baseline, after three, six and nine months. RESULTS: After three month training period, in the Nordic Walking group time spent walking and standing as well as intensity of walking increased (Delta walking time: +14.9 +/- 1.9 min/day; Delta standing time: +129 +/- 26 min/day; Delta movement intensity: +0.40 +/- 0.14 m/s2) while time spent sitting decreased (Delta sitting time: -128 +/- 15 min/day) compared to baseline (all: p &lt; 0.01) as well as compared to controls (all: p &lt; 0.01). Furthermore, 6MWD significantly increased compared to baseline (Delta 6MWD: +79 +/- 28 meters) as well as compared to controls (both: p &lt; 0.01). These significant improvements were sustained six and nine months after baseline. In contrast, controls showed unchanged daily physical activities and 6MWD compared to baseline for all time points. CONCLUSIONS: Nordic Walking is a feasible, simple and effective physical training modality in COPD. In addition, Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation. CLINICAL TRIAL REGISTRATION: Nordic Walking improves daily physical activities in COPD: a randomised controlled trial - ISRCTN31525632

Aero-Allergen Sensitization in the General Population: Longitudinal Analyses of the LEAD (Lung Heart Social Body) Study

BACKGROUND: Monitoring of sensitization may become a non-invasive marker of impaired epithelial barrier function related to changing environmental conditions. OBJECTIVE: To longitudinally evaluate the prevalence and associated factors for positive skin prick tests (SPT) in a general population cohort. METHODS: Baseline and 4-year follow-up data from the longitudinal LEAD study are used for the current analyses. Risk factors for SPT were analyzed by multivariate binary logistic regression analyses, including residence (urban/rural), sex, socioeconomic status (SES), allergic and/or respiratory diseases, lung function testing, blood eosinophils, body composition, lifestyle habits, family history, pets in household, and exposure to tobacco smoke in childhood/adolescence (6–18 years) and adulthood (≥19 years). RESULTS: In total, 1439 children/adolescents and 9844 adults with valid SPTs were included in these analyses. The prevalence of sensitization at baseline was 37.6% and was higher in males in every age group, except 10–<15 years. Individuals with doctor´s diagnosed allergy, asthma or parental allergy were more likely to have a positive SPT; in adulthood, sensitization was more common in those with a high SES. A lower occurrence of sensitization was associated with the presence of a dog in the household in childhood/adolescence and with smoking in adulthood. The prevalence and intensity (number of positive SPT reactions) increased after a 4-year follow-up, especially in children/adolescents. CONCLUSION: Sensitization is common in the general Austrian population and more likely in males than females. Longitudinal monitoring of sensitization in children/adolescents may identify environmental triggers related to changes in urbanization, industrialization and domestic lifestyle. ClinicalTrials.gov NCT01727518