Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma? A description of the protocol for the Breathing Together study

Acknowledgements The authors are indebted to the participants and parents who have already been recruited. We also acknowledge the enthusiasm and endeavour of the research nurse team which includes: Stephen Main, Margaret Connon, Catherine Beveridge, Julie Baggott, Kay Riding, Ellie McCamie, Maria Larsson, Lynda Melvin, Mumtaz Idris, Tara Murray, Nicky Tongue, Nicolene Plaatjies, Sheila Mortimer, Sally Spedding, Susy Grevatt, Victoria Welch, Morag Zelisko, Jillian Doherty, Jane Martin, Emma Macleod and Cilla Snape. We are also delighted to be working alongside the following colleagues in laboratories: Marie Craigon, Marie McWilliam, Maria Zarconi, Judit Barabas, Lindsay Broadbent, Ceyda Oksel and Sheerien Manzoor. Grant information The study is supported by the Wellcome Trust [108818]; and the PHA HSC R&D Division, Northern Ireland.Peer reviewedPublisher PD

Inequity in colorectal cancer treatment and outcomes: a population-based study

Several uncertainties surround optimal management of colorectal cancer. We investigated treatment patterns and factors influencing treatment receipt and mortality in routine clinical practice. We included 15 249 individuals, recorded by the National Cancer Registry (Ireland), with primary invasive colon or rectal tumours, diagnosed during 1994–2002. Logistic regression and Cox proportional hazards were used to determine factors associated with treatment receipt within 1 year of diagnosis and with mortality, respectively. A total of 78% had colorectal resection, 31% chemotherapy, and 13% radiotherapy (4% colon; 28% rectum). Half of stage IV patients underwent resection. Chemotherapy and radiotherapy use increased by at least 10% per annum. There was a notable increase in pre-operative radiotherapy from 2000 onwards. Patient-related factors were significantly associated with treatment receipt. Patients who were male, older, not married, or smokers had significantly higher risks of death. Chemotherapy was significantly associated with lower mortality for stage III, but not stage II, colon cancer. For rectal cancer, pre-operative radiotherapy was associated with reduced mortality. Surgery and chemotherapy were associated with longer survival for stage IV patients. The observed inequities in treatment and outcomes suggest that there is potential for further dissemination of therapies in routine practice. Improving treatment availability overall, and equity, has the potential to reduce mortality

Mid-childhood fat mass and airflow limitation at 15 years: The mediating role of insulin resistance and C-reactive protein

Background: We previously reported an association of high fat mass levels from age 9 to 15 years with lower forced expiratory flow in 1 s (FEV1)/forced vital capacity (FVC) ratio (i.e., increased risk of airflow limitation) at 15 years. Here, we aimed to assess whether insulin resistance and C-reactive protein (CRP) at 15 years partially mediate this association. Methods: We included 2263 children from the UK Avon Longitudinal Study of Parents and Children population-based cohort (ALSPAC). Four fat mass index (FMI) trajectories (“low,” “medium-low,” “medium-high,” “high”) from 9 to 15 years were previously identified using Group-Based Trajectory Modeling. Data on CRP, glucose, insulin, and post-bronchodilator FEV1/FVC were available at 15 years. We defined insulin resistance by the homeostasis model assessment-estimated insulin resistance index (HOMA-IR). We used adjusted linear regression models and a causal mediation analysis to assess the mediating role of HOMA-IR and CRP. Results: Compared to children in the “low” FMI trajectory, children in the “medium-high” and “high” FMI trajectories had lower FEV1/FVC at 15 years. The percentage of the total effect explained by HOMA-IR was 19.8% [−114.1 to 170.0] and 20.4% [1.6 to 69.0] for the “medium-high” and “high” trajectories, respectively. In contrast, there was little evidence for a mediating role of CRP. Conclusion: The association between mid-childhood fat mass and FEV1/FVC ratio at 15 years may be partially mediated by insulin resistance

Body mass index and weight change are associated with adult lung function trajectories: The prospective ECRHS study

Background: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS). Methods: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations. Results: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV 1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<-0.25 kg/year) exhibited an attenuation of FVC and FEV 1 declines. We found no association between weight change profiles and FEV 1 /FVC decline. Conclusion: Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life

Correction to: Assessing real-world gait with digital technology? Validation, insights and recommendations from the Mobilise-D consortium (<em>Journal of NeuroEngineering and Rehabilitation</em>, (2023), 20, 1, (78), 10.1186/s12984-023-01198-5)

\ua9 The Author(s) 2024.Following publication of the original article [1], the author noticed the errors in Table 1, and in Discussion section. In Table 1 under Metric (Gait sequence detection) column, the algorithms GSDB was updated with wrong description, input, output, language and citation and GSDc with wrong description has been corrected as shown below: (Table presented.) Description of algorithms for each metric: gait sequence detection (GSD), initial contact event detection (ICD), cadence estimation (CAD) and stride length estimation (SL) Metric Name Description Input Output Language References GSDA Based on a frequency-based approach, this algorithm is implemented on the vertical and anterior–posterior acceleration signals. First, these are band pass filtered to keep frequencies between 0.5 and 3 Hz. Next, a convolution of a 2 Hz sinewave (representing a template for a gait cycle) is performed, from which local maxima will be detected to define the regions of gait acc_v: vertical acceleration acc_ap: anterior–posterior acceleration WinS = 3 s; window size for convolution OL = 1.5 s; overlap of windows Activity_thresh = 0.01; Motion threshold Fs: sampling frequency Start: beginning of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector End: termination of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector Matlab\uae Iluz, Gazit [40] GSDB This algorithm, based on a time domain-approach, detects the gait periods based on identified steps. First, the norm of triaxial acceleration signal is low-pass filtered (FIR, fc = 3.2 Hz), then a peak detection procedure using a threshold of 0.1 [g] is applied to identify steps. Consecutive steps, detected using an adaptive step duration threshold are associated to gait sequences acc_norm: norm of the 3D-accelerometer signal Fs: sampling frequency th: peak detection threshold: 0.1 (g) Start: beginning of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector End: termination of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector Matlab\uae Paraschiv-Ionescu, Newman [41] GSDc This algorithm utilizes the same approach as GSDBthe only difference being a different threshold for peak detection of 0.15 [g] acc_norm: norm of the 3D-accelerometer signal Fs: sampling frequency th: peak detection threshold: 0.15 (g) Start: beginning of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector End: termination of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector Matlab\uae Paraschiv-Ionescu, Newman [41] In Discussion section, the paragraph should read as "Based on our findings collectively, we recommend using GSDB on cohorts with slower gait speeds and substantial gait impairments (e.g., proximal femoral fracture). This may be because this algorithm is based on the acceleration norm (overall accelerometry signal rather than a specific axis/direction (e.g., vertical), hence it is more robust to sensor misalignments that are common in unsupervised real-life settings. Moreover, the use of adaptive threshold, that are derived from the features of a subject’s data and applied to step duration for detection of steps belonging to gait sequences, allows increased robustness of the algorithm to irregular and unstable gait patterns" instead of “Based on our findings collectively, we recommend using GSDB on cohorts with slower gait speeds and substantial gait impairments (e.g., proximal femoral fracture). This may be because this algorithm is based on the acceleration norm (overall accelerometry signal rather than a specific axis/direction (e.g., vertical), hence it is more robust to sensor misalignments that are common in unsupervised real-life settings [41]. Moreover, the use of adaptive thresholds, that are derived from the features of a subject’s data and applied to the amplitude of acceleration norm and to step duration for detection of steps belonging to gait sequences, allows increased robustness of the algorithm to irregular and unstable gait patterns”

Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis.

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO\u2082, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV\u2081) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 \u3bcg\ub7m(-3) increase in NO\u2082 exposure was associated with lower levels of FEV\u2081 (-14.0 mL, 95% CI -25.8 to -2.1) and FVC (-14.9 mL, 95% CI -28.7 to -1.1). An increase of 10 \u3bcg\ub7m(-3) in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV\u2081 (-44.6 mL, 95% CI -85.4 to -3.8) and FVC (-59.0 mL, 95% CI -112.3 to -5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe

A three-generation study on the association of tobacco smoking with asthma

Background: Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma. Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged <= 51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines. Results: Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01-2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01-1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17-2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02-1.55). Conclusions: Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception