Epigenome-Wide Association Studies of Chronic Obstructive Pulmonary Disease and Lung Function: A Systematic Review.

Rationale: Chronic obstructive pulmonary disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as DNA methylation. Objectives: To systematically review the evidence form epigenome-wide association studies related to COPD and lung function. Methods: A systematic literature search performed on PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases identified 1,947 articles that investigated epigenetic changes associated with COPD and/or lung function; 17 of them met our eligibility criteria, from which data were manually extracted. Differentially methylated positions (DMPs) and/or annotated genes were considered replicated if identified by two or more studies with a P < 1 × 10-4. Measurements and Main Results: Ten studies profiled DNA methylation changes in blood and seven in respiratory samples, including surgically resected lung tissue (n = 3), small airway epithelial brushings (n = 2), BAL (n = 1), and sputum (n = 1). Main results showed: 1) high variability in study design, covariates, and effect sizes, which prevented a formal meta-analysis; 2) in blood samples, 51 DMPs were replicated in relation to lung function and 12 related to COPD; 3) in respiratory samples, 42 DMPs were replicated in relation to COPD but none in relation to lung function; and 4) in COPD versus control studies, 123 genes (2.6% of total) were shared between one or more blood and one or more respiratory samples and associated with chronic inflammation, ion transport, and coagulation. Conclusions: There is high heterogeneity across published COPD and/or lung function epigenome-wide association studies. A few genes (n = 123; 2.6%) were replicated in blood and respiratory samples, suggesting that blood can recapitulate some changes in respiratory tissues. These findings have implications for future research. Systematic Review [protocol] registered with Open Science Framework (OSF).

Are young children with asthma more likely to be less physically active?

BACKGROUND: Previous research suggests that children who experience asthma may be less physically active; however, results have been inconclusive. This study aimed to investigate whether the presence of asthma or wheeze is associated with lower physical activity levels in children, and whether sex, body mass index or earlier asthma or wheeze status modifies the association. METHODS: This study was conducted in 391 HealthNuts participants in Melbourne, Australia. Asthma and wheeze data were collected via questionnaire at age 4 and 6, and physical activity was measured through accelerometry. Using adjusted linear regression models, the cross-sectional and longitudinal associations were investigated. RESULTS: There was no evidence of a difference in time spent in moderate-to-vigorous physical activity (MVPA) at age 6 years between children with and without asthma at age 4; children with asthma spent 8.3 minutes more time physically active per day (95% CI: -5.6, 22.1, P = .24) than children without asthma. Similar results were seen for children with current wheeze (5.8 minutes per day more, 95% CI: -5.9, 17.5, P = .33) or ever wheeze or asthma (7.7 minutes per day more, 95% CI: -4.8, 20.2, P = .23) at age 4 years. Comparable null results were observed in the cross-sectional analyses. Interaction with BMI could not be assessed; however, previous asthma or wheeze status and sex were not found to modify these associations. CONCLUSION: This analysis found no evidence of asthma hindering physical activity in these young children. These results are encouraging, as they indicate that the Australian asthma and physical activity public health campaigns are being effectively communicated and adopted by the public.

Are adults with asthma less physically active? A systematic review and meta-analysis.

OBJECTIVE: To systematically review the evidence on whether having current, ever asthma and asthma control is associated with levels of total, moderate and vigorous physical activity. METHODS: We searched EMBASE, MEDLINE, and CINAHL databases, limiting searches to English language papers from inception until Oct 2019. We synthesized the evidence comparing levels of total, moderate and vigorous physical activity between adults with and without current asthma or ever asthma by random effects meta-analyses. RESULTS: A total of 25 studies were included, with 18 of these included in meta-analyses. A meta-analysis of 4 case-control studies found that adults with current asthma were less active, with 942.12 steps fewer per day, than adults without current asthma (SMD = -0.39, 95%CI: -0.54, -0.24, I2 = 0). Meta-analysis of four-high quality cross-sectional studies found that those with current or ever asthma were more likely to be inactive than those without asthma (binary OR current asthma = 0.85, 95%CI: 0.82, 0.89, I2 = 45.6%, and binary OR ever asthma = 0.83, 0.75, 0.91, I2 = 0, respectively). Meta-analysis, inclusive of all 10 cross-sectional studies with binary ORs, supported this finding. There was also some evidence that adults with current asthma and ever asthma (6 studies with categorical ORs) were less likely to exercise moderately and vigorously, but these meta-analyses were limited by high heterogeneity. No synthesis of the studies considering asthma control was possible. CONCLUSION: Adults with current or ever asthma had lower levels of total, moderate and vigorous physical activity than those without asthma and may be missing out on the health benefits of being physically active. The association between asthma control and physical activity warrants further investigation.

Predictors of lung function trajectories in population-based studies: A systematic review.

Despite the growing body of evidence on lung function trajectories over the life course and their risk factors, the literature has not been systematically synthesized. Publications related to lung function trajectories were identified from PubMed, EMBASE and CINAHL databases. Two authors independently identified publications for inclusion according to predefined selection criteria. Studies that modelled lung function trajectories and reported associated exposures were included. Meta-analyses could not be conducted due to heterogeneity in the exposures and methods used to model lung function trajectories. Nine publications were eligible for inclusion of which four used group-based trajectory modelling to model lung function trajectories, while five used latent profile analysis. Studies with repeated lung function measurements over the life course identified more trajectories than others. Only one study spanning from childhood to middle age reported catch-up trajectory. The following childhood risk factors for subnormal lung function trajectories were observed in at least across two studies: low birth weight, early wheezing, asthma, allergic sensitization, eczema, allergic rhinitis, lower respiratory tract infections, family history of asthma and second-hand smoke exposure. Adult active asthma and personal cigarette smoking were observed to be associated with accelerated decline lung trajectories. Our review identified 10 risk factors associated with the growth, catch-up, reduced plateau and decline trajectories of lung function. Intervention directed at childhood asthma and infections, and tobacco smoke exposure at all ages would help promote lung health and prevent subnormal lung function trajectories.

Backyard benefits? A cross-sectional study of yard size and greenness and children's physical activity and outdoor play.

BACKGROUND: The home environment is the most important location in young children's lives, yet few studies have examined the relationship between the outdoor home environment and child physical activity levels, and even fewer have used objectively measured exposures and outcomes. This study examined relationships between objectively assessed home yard size and greenness, and child physical activity and outdoor play. METHODS: Data were drawn from the HealthNuts study, a longitudinal study of 5276 children in Melbourne, Australia. We used cross-sectional data from a sample at Wave 3 (2013-2016) when participants were aged 6 years (n = 1648). A sub-sample of 391 children had valid accelerometer data collected from Tri-axial GENEActive accelerometers worn on their non-dominant wrist for 8 consecutive days. Yard area and greenness were calculated using geographic information systems. Objective outcome measures were minutes/day in sedentary, light, and moderate-vigorous physical activity (weekday and weekend separately). Parent-reported outcome measures were minutes/day playing outdoors (weekend and weekday combined). Multi-level regression models (adjusted for child's sex, mother's age at the birth of child, neighbourhood socioeconomic index, maternal education, and maternal ethnicity) estimated effects of yard size and greenness on physical activity. RESULTS: Data were available on outdoor play for 1648 children and usable accelerometer data for 391. Associations between yard size/greenness and components of physical activity were minimal. For example, during weekdays, yard size was not associated with daily minutes in sedentary behaviour (ß: 2.4, 95% CI: - 6.2, 11.0), light physical activity (ß: 1.4, 95% CI: - 5.7, 8.5) or MVPA (ß: -2.4, 95% CI: - 6.5, 1.7), with similar patterns at weekends. There was no relationship between median annual yard greenness and physical activity or play. CONCLUSION: In our study of young children residing in higher socio-economic areas of Melbourne yard characteristics did not appear to have a major impact on children's physical activity. Larger studies with greater variation in yard characteristics and identification of activity location are needed to better understand the importance of home outdoor spaces and guide sustainable city planning.

Does physical activity strengthen lungs and protect against asthma in childhood? A systematic review.

BACKGROUND: Physical activity may be a potentially modifiable risk factor for asthma and driver of lung function development. This systematic review aimed to summarize the available evidence concerning the longitudinal effect of physical activity on the development of asthma, the persistence of asthma symptoms and lung function outcomes in children and adolescents. METHODS: PubMed and Embase electronic databases were searched for all original articles that investigated the longitudinal association between physical activity and asthma outcomes or lung function outcomes in children and adolescents. The search and data extraction were conducted by two independent researchers. The methodological quality of the included studies was assessed using two critical assessment tools. RESULTS: The literature search retrieved 2298 publications from the electronic databases. All articles were screened, and 2289 were subsequently excluded, resulting in nine longitudinal studies eligible for inclusion in this review. Two studies found no association with incident wheeze, and two of four found no association with various asthma outcomes. Three studies investigated the effect on lung function: one observed an association in boys only, one observed an association in girls only, and one found no associations. CONCLUSION: The evidence was highly inconsistent for the relationship between physical activity and asthma and lung function outcomes. Hence, we conclude that there is insufficient evidence to suggest that physical activity has a long-term effect on the risk of asthma development in youth. Furthermore, there is insufficient evidence to determine the longitudinal effects of physical activity on lung function in children.

Bidirectional associations between diet and body composition measures from 2 to 15 years: Longitudinal Study of Australian Children.

This study investigates how dietary patterns and scores are associated with subsequent BMI and waist:height ratio (WHtR), and how BMI and WHtR are associated with subsequent dietary patterns or scores, from 2-3 to 10-11 and 4-5 to 14-15 years of age. In the Longitudinal Study of Australian Children, height, weight and waist circumference were measured biennially in children, yielding BMI z-score and WHtR. Parents, latterly children, reported frequency of child consumption of 12-16 food/drink items during the previous 24 h. At each wave, we empirically derived dietary patterns using factor analyses, and dietary scores based on the 2013 Australian Dietary Guidelines. We used structural-equation modelling to investigate cross-lagged associations (n 1972-2882) between diet and body composition measures in univariable and multivariable analyses. Dietary scores/patterns did not consistently predict WHtR and BMI z-score in the next wave, nor did BMI z-score and WHtR consistently predict diet in the next wave. The few associations seen were weak and often in the opposite direction to that hypothesised. The largest effect, associated with each standard deviation increase in BMI in wave 5 of the K cohort (age 12-13 years), was a 0·06 standard deviation estimated mean increase in dietary score (higher quality diet) in the subsequent wave (95 % CI 0·02, 0·11, P=0·003). Associations between dietary patterns/scores and body composition were not strongly evident in either direction. Better quantitative childhood dietary tools feasible for large-scale administration are needed to quantify how dietary patterns, energy intake and anthropometry co-develop.

The difference in amount of physical activity performed by children with and without asthma: A systematic review and meta-analysis.

OBJECTIVE: Despite the benefits of a physically active lifestyle, some studies suggest fear of exacerbations by both children and their parents limit physical activity in children with asthma. We undertook a systematic review to quantify the difference in objectively measured physical activity levels of children and adolescents with and without asthma. DATA SOURCES: MEDLINE, PubMed and EMBASE. STUDY SELECTION: English language observational studies of children and adolescents to the age of 18 that compared objectively measured physical activity (accelerometer or pedometer devices) between those with asthma and without asthma. RESULTS: Overall 22,285 articles were retrieved with 12 studies being included in the review: 1 cohort, 1 case-control and 10 cross-sectional. A meta-analysis of accelerometry data from the single cohort study and 8 cross-sectional studies produced an overall mean difference of 0.01 (95% CI: -0.09-0.11) activity counts per minute in children and adolescents without asthma compared to those with asthma. CONCLUSION: We did not find any evidence that children and adolescents with and without asthma engaged in different amounts of physical activity when measured objectively by accelerometers. Children and adolescents with asthma may not require differentially targeted policies to encourage more physical activity, however further longitudinal studies are needed.

The effects of weight change from childhood to adulthood on depression and anxiety risk in adulthood: A systematic review.

This review aimed to evaluate the effects of weight change from childhood to adulthood on depression and/or anxiety risk in adulthood. We systematically searched MEDLINE, PsychINFO, Embase, Cumulative Index to Nursing and Allied Health Literature, and Scopus for longitudinal studies assessing changes in weight status between childhood (≤18 years) and adulthood (≥19 years) in association with outcomes of depression and/or anxiety in adulthood. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale, and data were narratively synthesized. Seventeen articles met our inclusion criteria: 13 evaluated outcomes of depression, one evaluated outcomes of anxiety, and five evaluated composite measures of depression and anxiety. Evidence was most consistent regarding outcomes of depression, with most finding that persistent and/or increasing adiposity from childhood to adulthood is associated with an increased risk of depression, particularly in women. However, heterogeneity and limitations in the evidence preclude definitive conclusions and inconsistent findings were reported in the few studies that assessed anxiety and composite outcomes. Overall, it appears that early intervention to both prevent or resolve excess weight may aid in reducing the burden of depression, along with mental health support targeting adolescents with persistent and/or increasing adiposity. However, further high-quality research is needed to address the methodological limitations discussed.

The long-term effects of childhood adiposity on depression and anxiety in adulthood: A systematic review.

OBJECTIVE: This review aimed to evaluate the association between childhood adiposity and depression and anxiety risk in adulthood. METHODS: MEDLINE, PsychInfo, Embase, CINAHL, and Scopus were searched on June 6, 2022, to identify studies that investigated the association between childhood weight status (age ≤18 years) and outcomes of depression and/or anxiety in adulthood (age ≥19 years). Study quality was assessed using the Newcastle-Ottawa Scale and results were narratively synthesized. RESULTS: Sixteen studies were eligible for inclusion, with heterogeneity in methods and follow-up durations complicating comparisons. Six out of eight studies found a statistically significant association between childhood adiposity and increased likelihood of depression in adulthood, particularly in females. However, overall evidence was of moderate quality and study limitations prevented causal conclusions. In contrast, limited evidence and mixed findings were reported for the associations between childhood adiposity and depressive symptom severity or anxiety outcomes in adulthood. CONCLUSIONS: Evidence suggests that childhood adiposity is associated with greater vulnerability to depression in adulthood, particularly in females. However, further research is warranted to address the limitations discussed. Future research should also explore how changes in weight status from childhood to adulthood might differentially influence the likelihood of depression.

The longitudinal association between physical activity, strength and fitness, and lung function: A UK Biobank cohort study.

BACKGROUND: While physical activity is hypothesized to slow lung-function decline, the evidence is limited at a population level. This study investigated the longitudinal association between physical activity and related measures (grip strength, cardiovascular fitness) and lung function decline. METHODS: 20,111 UK Biobank cohort participants with lung function measures at baseline (2006-2010) and follow-up (2012-2014) were included. Physical activity (International Physical Activity Questionnaire: low, moderate, high categories), grip strength (dynamometer) and cardiovascular fitness (subsample, submaximal stationary bicycle) data were collected. Linear regression was utilized to assess the effect on follow-up FEV1, FVC, FEV1/FVC ratio (as decline in ml/yr and as z-scores) adjusting for baseline lung function and confounders. RESULTS: After 6.3 years mean follow-up, the decline in mean FEV1 and FVC was 30 ml/year and 38 ml/year respectively (n = 20,111). Consistent low physical activity (across baseline and follow-up) was associated with accelerated decline in FEV1 z-score (-0.119, 95 % Confidence Interval (CI) -0.168, -0.071, n = 16,900) and FVC z-score (-0.133, 95%CI -0.178, -0.088, n = 16,832). Accelerated decline in FEV1 z-scores was observed with decreasing baseline grip strength (-0.029, -95%CI -0.034, -0.024, n = 19,903), and with less strong evidence, decreasing fitness (-0.024, 95%CI -0.070, 0.022, n = 3048). CONCLUSION: This is the largest ever study to date to identify that lower physical activity, grip strength, and potentially cardiovascular fitness over time is associated with accelerated lung function decline. Although the effect sizes appear modest, such changes at population levels can have a substantial overall impact. This study provides evidence for adding 'lung health benefits' to the current physical activity guidelines.

Is asthma associated with COVID-19 infection? A UK Biobank analysis.

BACKGROUND: The relationship between asthma and coronavirus disease 2019 (COVID-19) risk is not clear and may be influenced by level of airway obstruction, asthma medication and known COVID-19 risk factors. We aimed to investigate COVID-19 risk in people with asthma. METHODS: We used UK Biobank data from all participants tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n=107 412; 17 979 test positive). Questions at baseline defined ever asthma and asthma medications. Baseline forced expiratory volume in 1 s (FEV1) was categorised into quartiles. Logistic regression modelled relationships between asthma, and asthma categories (age at onset, medications, FEV1 quartiles), and risk of SARS-CoV-2 positive test. We investigated modification by sex, ethnic group, smoking and body mass index. RESULTS: There was a reduced risk of a positive test associated with early-onset asthma (<13 years) (OR 0.91, 95% CI 0.84-0.99). This was found for participants with early-onset asthma who were male (OR 0.87, 95% CI 0.78-0.98), nonsmokers (OR 0.87, 95% CI 0.78-0.98), overweight/obese (OR 0.85, 95% CI 0.77-0.93) and non-Black (OR 0.90, 95% CI 0.82-0.98). There was increased risk amongst early-onset individuals with asthma in the highest compared to lowest quartile of lung function (1.44, 1.05-1.72). CONCLUSION: Amongst male, nonsmoking, overweight/obese and non-Black participants, having early-onset asthma was associated with lower risk of a SARS-CoV-2 positive test. We found no evidence of a protective effect from asthma medication. Individuals with early-onset asthma of normal weight and with better lung function may have lifestyle differences placing them at higher risk. Further research is needed to elucidate the contribution of asthma pathophysiology and different health-related behaviour, across population groups, to the observed risks.

Lung function trajectory and biomarkers in the Tasmanian Longitudinal Health Study.

BACKGROUND AND OBJECTIVE: Different lung function trajectories through life can lead to COPD in adulthood. This study investigated whether circulating levels of biomarkers can differentiate those with accelerated (AD) from normal decline (ND) trajectories. METHODS: The Tasmanian Longitudinal Health Study (TAHS) is a general population study that measured spirometry and followed up participants from ages 7 to 53 years. Based on their forced expiratory volume in 1 s (FEV1) trajectories from age 7 to 53 years, this analysis included those with COPD at age 53 years (60 with AD and 94 with ND) and controls (n=720) defined as never-smokers with an average FEV1 trajectory. Circulating levels of selected biomarkers determined at 53 and 45 years of age were compared between trajectories. RESULTS: Results showed that CC16 levels (an anti-inflammatory protein) were lower and C-reactive protein (CRP) (a pro-inflammatory marker) higher in the AD than in the ND trajectory. Higher CC16 levels were associated with a decreased risk of belonging to the AD trajectory (OR=0.79 (0.63-0.98) per unit increase) relative to ND trajectory. Higher CRP levels were associated with an increased risk of belonging to the AD trajectory (OR=1.07, 95% CI: 1.00-1.13, per unit increase). Levels of CC16 (area under the curve (AUC)=0.69, 95% CI: 0.56-0.81, p=0.002), CRP (AUC=0.63, 95% CI: 0.53-0.72, p=0.01) and the combination of both (AUC=0.72, 95% CI: 0.60-0.83, p<0.001) were able to discriminate between the AD and ND trajectories. Other quantified biomarkers (interleukin (IL)-4, IL-5, IL-6, IL-10 and tumour necrosis factor-α (TNF-α)) were not significantly different between AD, ND and controls. CONCLUSIONS: Circulating levels of CRP and CC16 measured in late adulthood identify different lung function trajectories (AD versus ND) leading to COPD at age 53 years.

Trajectories of asthma and allergies from 7 years to 53 years and associations with lung function and extrapulmonary comorbidity profiles: a prospective cohort study.

BACKGROUND: Longitudinal trajectories of asthma and allergies from childhood to adulthood might be differentially associated with lung function and chronic obstructive pulmonary disease (COPD), but associations with extrapulmonary comorbidities have not been well investigated. We aimed to assess these trajectories and examine their associations with lung function outcomes and profiles of comorbidities. METHODS: In this prospective cohort study, data for asthma and related allergic conditions (ie, eczema, hay fever, and food allergy) were prospectively collected from the Tasmanian Longitudinal Health Study for participants aged 7-53 years originally recruited in Tasmania, Australia. All surviving individuals in the database with contact details were invited in the most recent follow-up (mean age 53 years). There were no exclusion criteria. With use of latent class analysis, we identified longitudinal trajectories of asthma and allergic conditions from 7-53 years, and profiles of self-reported extrapulmonary conditions recorded at 53 years. The associations between asthma and allergy trajectories and morbidity profiles and lung function at 53 years were investigated with regression models. FINDINGS: Between Sept 3, 2012, and Nov 8, 2016, of 6128 individuals invited, 3609 (58·9%) individuals were enrolled. We identified five asthma and allergy trajectories: minimal and least asthma and allergies (n= 1767 [49·0%]); late-onset hay fever, no asthma (n=1065 [29·5%]); early-onset remitted asthma and allergies (n=236 [6·5%]); late-onset asthma and allergies (n=317 [8·8%]); and early-onset persistent asthma and allergies (n=224 [6·2%]); and four profiles of extrapulmonary morbidities: minimal or least disease (n=2206 [61·1%]); dominant mental health disorders (n=861 [23·9%]); dominant cardiovascular diseases or risks (n=424 [11·7%]); and multiple disorders (n=117 [3·2%]). The late-onset asthma and allergies trajectory was predominantly associated with the multiple disorders profile (relative risk ratio 3·3 [95% CI 1·9-5·9]), whereas the other asthma and allergy trajectories were associated only with the dominant mental health disorders profile. Both spirometrically defined and clinical COPD were most strongly associated with the early-onset persistent asthma and allergies trajectory (odds ratio [OR] 5·3 [95% CI 3·2-8·6]) and also with the late-onset asthma and allergies trajectory (OR 3·8 [2·4-6·1]). INTERPRETATION: Distinct longitudinal trajectories of asthma and allergic disease from childhood to 53 years are associated with different profiles of extrapulmonary comorbidities and varying risk of COPD. These findings can inform a personalised approach in clinical guidelines and management focusing on treatable traits. Comorbidity profiles are a new target for early identification and intervention. FUNDING: National Health and Medical Research Council of Australia, EU's Horizon 2020, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline.

The Association of Early Life Viral Respiratory Illness and Atopy on Asthma in Children: Systematic Review and Meta-Analysis.

BACKGROUND: The interaction between early life viral respiratory illness and atopy in the genesis of asthma has been widely discussed in the literature as the "two-hit hypothesis." OBJECTIVE: To synthesize evidence regarding the association of childhood viral respiratory illness and atopy in the development of persistent wheezing and asthma. METHODS: A systematic review was performed, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Human studies investigating early life associations between atopy and viral respiratory illness with outcomes of asthma and wheezing were included. Meta-analysis was performed to investigate the association of viral illness across atopic and nonatopic groups. Subgroup analysis was undertaken to investigate potential effect modification of age at outcome. RESULTS: Nine cohort studies were included, with data available for meta-analysis in 4 birth cohort studies. There was a stronger association of viral respiratory illness with persistent asthma/wheeze in atopic (odds ratio [OR], 4.02; 95% CI, 1.46-11.06) compared with nonatopic (OR, 2.32; 95% CI, 1.22-4.40) individuals; however, the evidence for this was limited. In 3 studies amenable to subanalysis based on outcome age, a stronger effect was observed up to 7 years for those with atopy (OR, 7.27; 95% CI 4.65-11.36) compared with those without atopy (OR, 3.19; 95% CI, 2.09-4.87). CONCLUSIONS: There was a stronger association between viral respiratory illness and asthma/wheeze outcomes in individuals with atopy as compared with those without atopy. When outcomes were considered at younger ages, a greater differential effect was observed. Within the limitations of the few available studies however, definite conclusions cannot be made. There was also insufficient evidence for differential effects of early versus late atopy. Further research, in particular regarding virus type, timing of atopy, and atopic phenotype, would contribute to untangling this complex association.

Physical activity and asthma: cause or consequence? A bidirectional longitudinal analysis.

BACKGROUND: There is increasing interest in the role physical activity (PA) can play in the development and management of asthma. Understanding whether PA can have a positive effect is hindered by the potential influence of asthma on PA and a lack of relevant longitudinal data, leading to a debate on the existence and direction of these links. The aim of this study was to explore whether having asthma results in lower PA levels, and/or whether lower PA levels lead to more asthma in children and adolescents. METHODS: In a population-based study of 4983 children, data on asthma and PA were collected via questionnaires and time use diaries biennially, between the ages of 6 and 14. Current asthma was defined as use of asthma medications or wheeze in the past year, and incident asthma was defined as doctor's diagnosis since the previous wave. PA was time spent doing moderate-to-vigorous physical activities in a day. Bidirectionality of this relationship was investigated using cross-lagged structural equational models. RESULTS: PA was not longitudinally associated with incident or current asthma. Similarly, there was no evidence that incident or current asthma predicted PA at any of the ages. CONCLUSIONS: Using a novel strategy to investigate bidirectionality between PA and asthma, our results suggest that asthma and PA participation are not longitudinally associated in either direction. Our findings suggest that PA does not play an important role in the development or persistence of asthma.

Validity of the Berlin questionnaire in detecting obstructive sleep apnea: A systematic review and meta-analysis.

We aimed to systematically review the Berlin questionnaire as a screening tool for obstructive sleep apnea. We systematically searched PubMed, Embase, and Scopus databases, reviewed articles reporting the Berlin questionnaire's diagnostic utility as measured against type-1 polysomnography, and performed meta-analyses where possible. Thirty five eligible articles showed that the Berlin questionnaire's diagnostic utility varied by study population, definition of hypopnea used, and apnea-hypopnea index threshold used. It had good sensitivity and specificity for detecting clinically relevant obstructive sleep apnea as well as any obstructive sleep apnea in the sleep clinic population. Despite limited evidence, it showed modest to high sensitivity for detecting clinically relevant obstructive sleep apnea or any obstructive sleep apnea in other clinical and general population subgroups. Its specificity was relatively low. Possible reasons for variability in reported diagnostic utility of the Berlin questionnaire are multifaceted. We conclude that the Berlin questionnaire is useful as a clinical screening test and epidemiological tool in the sleep clinic population. Despite limited evidence, it likely has potential clinical and research utility in other populations. Adopting more consistent methodological definitions and focussing more on the general population and specific clinical populations to determine its usefulness as a clinical or epidemiological screening tool are recommended.