Distinct trajectories of lung function from childhood to mid-adulthood.

RATIONALE: Life course trajectories of lung function development and decline influence the risk for lung disease but are poorly documented. OBJECTIVE: To document lung function trajectories from childhood to mid-adult life. METHODS: We modelled forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC at ages 9, 11, 13, 15, 18, 21, 26, 32, 38 and 45 years from a population-based cohort using latent profile analysis to identify distinct subgroups of participants with similar lung function trajectories. Regression analyses were used to assess associations between the trajectories, early life factors and postbronchodilator airflow obstruction at age 45. RESULTS: Among 865 participants with ≥6 measures of lung function, we identified 10 distinct FEV1 trajectories. Most were approximately parallel except for a childhood airway hyper-responsiveness-related persistently low trajectory (3% of study population); two accelerated-decline trajectories, one of which (8%) was associated with smoking and higher adult body mass index (BMI) and a catch-up trajectory (8%). Findings for FEV1/FVC trajectories were similar. Nine trajectories were identified for FVC: most were also approximately parallel except for a higher BMI-related accelerated-decline trajectory. The three FEV1 trajectories leading to the lowest FEV1 values comprised 19% of the cohort but contributed 55% of airflow obstruction at age 45. CONCLUSIONS: Lung function trajectories to mid-adult life are largely established before adolescence, with a few exceptions: a childhood airway hyper-responsiveness-related persistently low trajectory, which starts low and gets worse with age, and accelerated adult decline trajectories associated with smoking and obesity. Adverse trajectories are associated with a high risk of airflow obstruction in mid-adult life.

Body composition and respiratory outcomes in children: a population-based prospective cohort study.

BACKGROUND: Body composition might influence lung function and asthma in children, but its longitudinal relations are unclear. We aimed to identify critical periods for body composition changes during childhood and adolescence in relation to respiratory outcomes in adolescents. METHODS: In a population-based prospective cohort study, we measured body mass index, fat mass index (FMI), lean mass index (LMI) and the ratio of android fat mass divided by gynoid fat mass (A/G ratio) by dual-energy X-ray absorptiometry at 6, 10 and 13 years. At 13 years, lung function was measured by spirometry, and current asthma was assessed by questionnaire. RESULTS: Most prominently and consistently, higher FMI and A/G ratio at age 13 years were associated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and forced expiratory flow after exhaling 75% of FVC (FEF75) (range Z-score difference -0.13 (95% CI -0.16 to -0.10) to -0.08 (95% CI -0.11 to -0.05) per SD score increase), and higher LMI at all ages was associated with higher FEF75 (range Z-score difference 0.05 (95% CI 0.01 to 0.08) to 0.09 (95% CI 0.06 to 0.13)). Between the ages of 6 and 13 years, normal to high FMI and A/G ratio were associated with lower FEV1/FVC and FEF75 (range Z-score difference -0.20 (95% CI -0.30 to -0.10) to -0.17 (95% CI -0.28 to -0.06)) and high to high LMI with higher FEF75 (range Z-score difference0.32 (95% CI 0.23 to 0.41)). Body composition changes were not associated with asthma. CONCLUSION: Adolescents with higher total and abdominal fat indices may have impaired lung function, while those with a higher lean mass during childhood and adolescence may have better small airway function. Public health measures should focus on a healthy body composition in adolescents to minimise respiratory morbidity.

Influence of age on clinical characteristics, pharmacological management and exacerbations in children with asthma.

BACKGROUND: Asthma trials and guidelines often do not distinguish between adolescents and younger children. Using a large English data set, we evaluated the impact of age on asthma characteristics, management and exacerbations. METHODS: Primary care medical records, 2004-2021, were linked to hospital records. Children were categorised by age at diagnosis and followed until the next age bracket. Ages (based on management guidelines) were 5-8 years, 9-11 years and adolescents (12-16 years). Characteristics evaluated included body mass index, allergies and events before and after diagnosis (symptoms, medication). Exacerbation incidence was calculated. Multivariable Cox proportional hazards determined associations with exacerbations. RESULTS: 119 611 children were eligible: 61 940 (51.8%) 5-8 years, 32 316 (27.7%) 9-11 years and 25 355 (21.2%) adolescents. Several characteristics differed by age; children aged 5-8 years had the highest proportion with eczema, food/drug allergy and cough, but adolescents had the highest proportion with overweight/obesity, aeroallergen sensitisation, dyspnoea and short-acting-beta-agonist only use. Exacerbation rates were highest in the youngest children (per 100 person-years (95% CI): 5-8 years =13.7 (13.4-13.9), 9-11 years =10.0 (9.8-10.4), adolescents =6.7 (6.5-7.0)). Exacerbation risk factors also differed by age; 5-8 years: male, eczema and food/drug allergy were strongly associated, but for children ≥9 years old, obesity and aeroallergen sensitisation were strongly associated. For all children, higher socioeconomic deprivation was significantly associated with having an exacerbation. Delayed diagnosis was most common in children aged 5-8 years and was associated with increased exacerbations across all ages. CONCLUSION: Children's baseline characteristics and exacerbation rates varied according to their age group. Clinical guidelines should consider age at time of diagnosis more discretely than the broad range, 5-16 years, as this appears to impact on asthma severity and management.

Impact of sex on severe asthma: a cross-sectional retrospective analysis of UK primary and specialist care.

INTRODUCTION: After puberty, females are more likely to develop asthma and in a more severe form than males. The associations between asthma and sex are complex with multiple intrinsic and external factors. AIM: To evaluate the sex differences in the characteristics and treatment of patients with severe asthma (SA) in a real-world setting. METHODS: Demographic, clinical and treatment characteristics for patients with SA in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD) were retrospectively analysed by sex using univariable and multivariable logistic regression analyses adjusted for year, age and hospital/practice. RESULTS: 3679 (60.9% female) patients from UKSAR and 18 369 patients (67.9% female) from OPCRD with SA were included. Females were more likely to be symptomatic with increased Asthma Control Questionnaire-6 (UKSAR adjusted OR (aOR) 1.14, 95% CI 1.09 to 1.18) and Royal College of Physicians-3 Question scores (OPCRD aOR 1.29, 95% CI 1.13 to 1.47). However, they had a higher forced expiratory volume in 1 second per cent (FEV1%) predicted (UKSAR 68.7% vs 64.8%, p<0.001) with no significant difference in peak expiratory flow. Type 2 biomarkers IgE (UKSAR 129 IU/mL vs 208 IU/mL, p<0.001) and FeNO (UKSAR 36ppb vs 46ppb, p<0.001) were lower in females with no significant difference in blood eosinophils or biological therapy. Females were less likely to be on maintenance oral corticosteroids (UKSAR aOR 0.86, 95% CI 0.75 to 0.99) but more likely to be obese (UKSAR aOR 1.67, 95% CI 145 to 1.93; OPCRD SA aOR 1.46, 95% CI 1.34 to 1.58). CONCLUSIONS: Females had increased symptoms and were more likely to be obese despite higher FEV1% predicted and lower type 2 biomarkers with consistent and clinically important differences across both datasets.

Clinical implications of airway obstruction with normal or low FEV1 in childhood and adolescence.

BACKGROUND: Airway obstruction is defined by spirometry as a low forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio. This impaired ratio may originate from a low FEV1 (classic) or a normal FEV1 in combination with a large FVC (dysanaptic). The clinical implications of dysanaptic obstruction during childhood and adolescence in the general population remain unclear. AIMS: To investigate the association between airway obstruction with a low or normal FEV1 in childhood and adolescence, and asthma, wheezing and bronchial hyperresponsiveness (BHR). METHODS: In the BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology; Sweden) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy; the Netherlands) birth cohorts, obstruction (FEV1:FVC ratio less than the lower limit of normal, LLN) at ages 8, 12 (PIAMA only) or 16 years was classified as classic (FEV1

Type-2 inflammation and lung function decline in chronic airway disease in the general population.

BACKGROUND: It is unclear if type-2 inflammation is associated with accelerated lung function decline in individuals with asthma and chronic obstructive pulmonary disease (COPD). We tested the hypothesis that type-2 inflammation indicated by elevated blood eosinophils (BE) and fraction of exhaled nitric oxide (FeNO) is associated with accelerated lung function decline in the general population. METHODS: We included adults from the Copenhagen General Population Study with measurements of BE (N=15 605) and FeNO (N=2583) from a follow-up examination and assessed forced expiratory volume in 1 s (FEV1) decline in the preceding 10 years. Based on pre- and post-bronchodilator lung function, smoking history and asthma at follow-up examination, participants were assigned as not having airway disease, asthma with full reversibility (AR), asthma with persistent obstruction (APO), COPD, and not classifiable airflow limitation (NAL). RESULTS: FEV1 decline in mL/year increased with 1.0 (95% CI 0.6 to 1.4, p<0.0001) per 100 cells/µL higher BE and with 3.2 (95% CI 2.0 to 4.5, p<0.0001) per 10 ppb higher FeNO. Adjusted FEV1 decline in mL/year was 18 (95% CI 17 to 20) in those with BE<300 cells/µL and FeNO<20 ppb, 22 (19-25) in BE≥300 cells/µL or FeNO≥20 ppb, and 27 (21-33) in those with BE≥300 cells/µL and FeNO≥20 ppb (p for trend<0.0001). Corresponding FEV1 declines were 24 (19-29), 33 (25-40) and 44 (31-56) in AR (0.002), 26 (14-37), 36 (12-60) and 56 (24-89) in APO (0.07), 32 (27-36), 31 (24-38) and 44 (24-65) in COPD (0.46), and 27 (21-33), 35 (26-45), and 37 (25-49) in NAL (0.10), respectively. CONCLUSIONS: Type-2 inflammation indicated by elevated BE and FeNO is associated with accelerated FEV1 decline in individuals with chronic airway disease in the general population, and this association was most pronounced in an asthma-like phenotype.

Association between socioeconomic deprivation, ethnicity and health outcomes in preschool children with recurrent wheeze in England: a retrospective cohort study.

BACKGROUND: Preschool-aged children have among the highest burden of acute wheeze. We investigated differences in healthcare use, treatment and outcomes for recurrent wheeze/asthma in preschoolers from different ethno-socioeconomic backgrounds. METHODS: Retrospective cohort study using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics in England. We reported number of acute presentations and hospitalisations stratified by index of multiple deprivation (IMD) and ethnicity; and factors associated with treatment non-escalation, and hospitalisation rates using multivariable logistic and Poisson regression models. RESULTS: 194 291 preschool children were included. In children not trialled on asthma preventer medications, children from the most deprived IMD quintile (adjusted OR 1.67; 95% CI 1.53 to 1.83) and South Asian (1.77; 1.64 to 1.91) children were more likely to have high reliever usage and where specialist referral had not occurred, the odds of referral being indicated was higher in the most deprived quintile (1.39; 1.28 to 1.52) and South Asian (1.86; 1.72 to 2.01) children compared with the least deprived quintile and white children, respectively.Hospitalisation rates for wheeze/asthma were significantly higher in children from the most deprived quintile (adjusted IRR 1.20; 95% CI 1.13 to 1.27) compared with the least, and in South Asian (1.57; 1.44 to 1.70) and black (1.32; 1.22 to 1.42) compared with white children. CONCLUSIONS: We identified inequalities in wheeze/asthma treatment and morbidity in preschool children from more deprived, and non-white backgrounds. A multifaceted approach to tackle health inequality at both the national and local levels, which includes a more integrated and standardised approach to treatment, is needed to improve health outcomes in children with preschool wheeze/asthma.

Asthma hospitalisations and heat exposure in England: a case-crossover study during 2002-2019.

BACKGROUND: Previous studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space. METHODS: We retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1 km×1 km resolution was retrieved from the UK Met Office. We focused on lag 0-3 days. We employed a case-crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays). RESULTS: After accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1°C increase in the ambient summer temperature. The effect was highest for males aged 16-64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable. CONCLUSION: This study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.

Long-term exposure to ambient air pollution and asthma symptom score in the CONSTANCES cohort.

BACKGROUND: The asthma symptom score allows to consider asthma as a continuum and to investigate its risk factors. One previous study has investigated the association between asthma score and air pollution and only for nitrogen dioxide (NO2). We aimed to study the associations between particulate matter with an aerodynamic diameter lower than 2.5 µm (PM2.5), black carbon (BC) and NO2 and the asthma symptom score in adults from CONSTANCES, a French population-based cohort. METHODS: Asthma symptom score (range: 0-5) was based on the number of five self-reported symptoms of asthma in the last 12 months. Annual individual exposure to PM2.5, BC and NO2 was estimated at participants' residential address using hybrid land-use regression models. Cross-sectional associations of each pollutant with asthma symptom score were estimated using negative binomial regressions adjusted for age, sex, smoking status and socioeconomic position. Associations with each symptom were estimated using logistic regression. The effect of BC independent of total PM2.5 was investigated with a residual model. RESULTS: Analyses were conducted on 135 165 participants (mean age: 47.2 years, 53.3% women, 19.0% smokers, 13.5% ever asthma). The ratio of mean score was 1.12 (95% CI 1.10 to 1.14), 1.14 (95% CI 1.12 to 1.16) and 1.12 (95% CI 1.10 to 1.14) per one IQR increase of PM2.5 (4.86 µg/m3), BC (0.88 10-5 m-1) and NO2 (17.3 µg/m3). Positive and significant associations were also found for each asthma symptom separately. BC effect persisted independently of total PM2.5. CONCLUSION: Exposure to each pollutant was associated with increased asthma symptom score in adults. This study highlights that BC could be one of the most harmful particulate matter components.

Paediatric asthma hospitalisations continue to decrease in Finland and Sweden between 2015 and 2020.

We previously reported a decreasing incidence of paediatric asthma hospitalisations in Finland, but a rather stable trend in Sweden, between 2005 and 2014. We now aimed to investigate the incidence of paediatric asthma hospitalisations in these countries between 2015 and 2020, using Finland's National Hospital Discharge Register and Sweden's National Patient Register, which cover all hospitalisations in the respective countries. From 2015 to 2019, the incidence of paediatric asthma hospitalisations decreased by 36.7% in Finland and by 39.9% in Sweden and are increasingly approaching parity. In 2020, despite differences in COVID-19-related restrictions, asthma hospitalisations decreased by over 40%, thus warranting future research on the subject.

Recent trends in asthma diagnosis, preschool wheeze diagnosis and asthma exacerbations in English children and adolescents: a SABINA Jr study.

BACKGROUND: Asthma-related burden remains poorly characterised in children in the UK. We quantified recent trends in asthma prevalence and burden in a UK population-based cohort (1‒17-year-olds). METHODS: The Clinical Practice Research Datalink Aurum database (2008‒2018) was used to assess annual asthma incidence and prevalence in 1‒17-year-olds and preschool wheeze in 1‒5-year-olds, stratified by sex and age. During the same period, annual asthma exacerbation rates were assessed in those with either a diagnosis of preschool wheeze or asthma. RESULTS: Annual asthma incidence rates decreased by 51% from 1403.4 (95% CI 1383.7 to 1423.2) in 2008 to 688.0 (95% CI 676.3 to 699.9) per 105 person-years (PYs) in 2018, with the most pronounced decrease observed in 1‒5-year olds (decreasing by 65%, from 2556.9 (95% CI 2509.8 to 2604.7) to 892.3 (95% CI 866.9 to 918.3) per 105 PYs). The corresponding decreases for the 6‒11- and 12‒17-year-olds were 36% (1139.9 (95% CI 1110.6 to 1169.7) to 739.9 (95% CI 720.5 to 759.8)) and 20% (572.3 (95% CI 550.4 to 594.9) to 459.5 (95% CI 442.9 to 476.4)) per 105 PYs, respectively. The incidence of preschool wheeze decreased over time and was slightly more pronounced in the 1‒3 year-olds than in the 4-year-olds. Prevalence of asthma and preschool wheeze also decreased over time, from 18.0% overall in 2008 to 10.2% in 2018 for asthma. Exacerbation rates increased over time from 1.33 (95% CI 1.31 to 1.35) per 10 PYs in 2008 to 1.81 (95% CI 1.78 to 1.83) per 10 PYs in 2018. CONCLUSION: Paediatric asthma incidence decreased in the UK since 2008, particularly in 1-5-year-olds; this was accompanied by a decline in asthma prevalence. Preschool wheeze incidence also decreased in this age group. However, exacerbation rates have been increasing.

Respiratory and allergic outcomes among 5-year-old children exposed to pesticides.

BACKGROUND: Little is known about the effects of pesticides on children's respiratory and allergic outcomes. We evaluated associations of prenatal and current pesticide exposures with respiratory and allergic outcomes in children from the Infants' Environmental Health Study in Costa Rica. METHODS: Among 5-year-old children (n=303), we measured prenatal and current specific gravity-corrected urinary metabolite concentrations of insecticides (chlorpyrifos, pyrethroids), fungicides (mancozeb, pyrimethanil, thiabendazole) and 2,4-D. We collected information from caregivers on respiratory (ever doctor-diagnosed asthma and lower respiratory tract infections (LRTI), wheeze and cough during last 12 months) and allergic (nasal allergies, itchy rash, ever eczema) outcomes. We fitted separate multivariable logistic regression models for high (≥75th percentile (P75)) vs low (

Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS.

INTRODUCTION: Obesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults. METHODS: We used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I (t) to ECRHS II (t+1), and from ECRHS II (t) to ECRHS III (t+1). We excluded obese (body mass index≥30 kg/m2) individuals at visit t. The relative risk (RR) of obesity at t+1 associated with asthma at t was estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity. RESULTS: We included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II-III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in ≤20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association. CONCLUSION: This is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids.

Air pollution associated with incidence and progression trajectory of chronic lung diseases: a population-based cohort study.

BACKGROUND: No prior study has examined the effects of air pollution on the progression from healthy to chronic lung disease, subsequent chronic lung multimorbidity and further to death. METHODS: We used data from the UK Biobank of 265 506 adults free of chronic lung disease at recruitment. Chronic lung multimorbidity was defined as the coexistence of at least two chronic lung diseases, including asthma, chronic obstructive pulmonary disease and lung cancer. The concentrations of air pollutants were estimated using land-use regression models. Multistate models were applied to assess the effect of air pollution on the progression of chronic lung multimorbidity. RESULTS: During a median follow-up of 11.9 years, 13 863 participants developed at least one chronic lung disease, 1055 developed chronic lung multimorbidity and 12 772 died. We observed differential associations of air pollution with different trajectories of chronic lung multimorbidity. Fine particulate matter showed the strongest association with all five transitions, with HRs (95% CI) per 5 µg/m3 increase of 1.31 (1.22 to 1.42) and 1.27 (1.01 to 1.57) for transitions from healthy to incident chronic lung disease and from incident chronic lung disease to chronic lung multimorbidity, and 1.32 (1.21 to 1.45), 1.24 (1.01 to 1.53) and 1.91 (1.14 to 3.20) for mortality risk from healthy, incident chronic lung disease and chronic lung multimorbidity, respectively. CONCLUSION: Our study provides the first evidence that ambient air pollution could affect the progression from free of chronic lung disease to incident chronic lung disease, chronic lung multimorbidity and death.

Plasma thymic stromal lymphopoietin (TSLP) in adults with non-severe asthma: the EGEA study.

Thymic stromal lymphopoietin (TSLP), a cytokine involved in severe asthma treatment, was never studied in non-severe asthma.Among 969 adults from a large epidemiological study, cross-sectional analyses showed that plasma TSLP levels were associated with increased age and BMI, male sex, smoking and high TSLP levels (one IQR increase) with current asthma and poor lung function. High TSLP levels were also associated with persistence of asthma attacks (aOR=2.14 (95% CI 1.23 to 3.72)) and dyspnoea (aOR=2.71 (95% CI 1.39 to 5.28)) 10 years later.Our results suggest that TSLP could be a cytokine of interest in non-severe asthma, and its determinants of circulating levels could be considered in asthma management.

Asthma symptoms, spirometry and air pollution exposure in schoolchildren in an informal settlement and an affluent area of Nairobi, Kenya.

BACKGROUND: Although 1 billion people live in informal (slum) settlements, the consequences for respiratory health of living in these settlements remain largely unknown. This study investigated whether children living in an informal settlement in Nairobi, Kenya are at increased risk of asthma symptoms. METHODS: Children attending schools in Mukuru (an informal settlement in Nairobi) and a more affluent area (Buruburu) were compared. Questionnaires quantified respiratory symptoms and environmental exposures; spirometry was performed; personal exposure to particulate matter (PM2.5) was estimated. RESULTS: 2373 children participated, 1277 in Mukuru (median age, IQR 11, 9-13 years, 53% girls), and 1096 in Buruburu (10, 8-12 years, 52% girls). Mukuru schoolchildren were from less affluent homes, had greater exposure to pollution sources and PM2.5. When compared with Buruburu schoolchildren, Mukuru schoolchildren had a greater prevalence of symptoms, 'current wheeze' (9.5% vs 6.4%, p=0.007) and 'trouble breathing' (16.3% vs 12.6%, p=0.01), and these symptoms were more severe and problematic. Diagnosed asthma was more common in Buruburu (2.8% vs 1.2%, p=0.004). Spirometry did not differ between Mukuru and Buruburu. Regardless of community, significant adverse associations were observed with self-reported exposure to 'vapours, dusts, gases, fumes', mosquito coil burning, adult smoker(s) in the home, refuse burning near homes and residential proximity to roads. CONCLUSION: Children living in informal settlements are more likely to develop wheezing symptoms consistent with asthma that are more severe but less likely to be diagnosed as asthma. Self-reported but not objectively measured air pollution exposure was associated with increased risk of asthma symptoms.

Examining the effect of the COVID-19 pandemic on community virus prevalence and healthcare utilisation reveals that peaks in asthma, COPD and respiratory tract infection occur with the re-emergence of rhino/enterovirus.

INTRODUCTION: Airway disease exacerbations are cyclical related to respiratory virus prevalence. The COVID-19 pandemic has been associated with reduced exacerbations possibly related to public health measures and their impact on non-COVID-19 respiratory viruses. We aimed to investigate the prevalence of non-COVID-19 respiratory viruses during the pandemic compared with prior in Ontario, Canada and healthcare utilisation related to asthma, chronic obstructive pulmonary disease (COPD) and respiratory tract infection. METHODS: This is a population-based retrospective analysis of respiratory virus tests, emergency department (ED) visits and hospitalisations between 2015 and 2021 in Ontario. Weekly virus testing data were used to estimate viral prevalence for all non-COVID-19 respiratory viruses. We plotted the %positivity and observed and expected counts of each virus to visualise the impact of the pandemic. We used Poisson and binomial logistic regression models to estimate the change in %positivity, count of positive viral cases and count of healthcare utilisation during the pandemic. RESULTS: The prevalence of all non-COVID-19 respiratory viruses decreased dramatically during the pandemic compared with prior. Comparing periods, the incidence rate ratio (IRR) for positive cases corresponded to a >90% reduction for non-COVID-19 respiratory viruses except adenovirus and rhino/enterovirus. Asthma-related ED visits and hospital admissions fell by 57% (IRR 0.43 (95% CI 0.37 to 0.48)) and 61% (IRR 0.39 (95% CI 0.33 to 0.46)). COPD-related ED visits and admissions fell by 63% (IRR 0.37 (95% CI 0.30 to 0.45)) and 45% (IRR 0.55 (95% CI 0.48 to 0.62)). Respiratory tract infection ED visits and admissions fell by 85% (IRR 0.15 (95% CI 0.10 to 0.22)), and 85% (IRR 0.15 (95% CI 0.09 to 0.24)). Rather than the usual peaks in disease condition, during the pandemic, healthcare utilisation peaked in October when rhino/enterovirus peaked. CONCLUSIONS: The prevalence of nearly all non-COVID-19 respiratory viruses decreased during the pandemic and was associated with marked reductions in ED visits and hospitalisations. The re-emergence of rhino/enterovirus was associated with increased healthcare utilisation.

Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease.

RATIONALE: Eosinophils are associated with airway inflammation in respiratory disease. Eosinophil production and survival is controlled partly by interleukin-5: anti-interleukin-5 agents reduce asthma and response correlates with baseline eosinophil counts. However, whether raised eosinophils are causally related to chronic obstructive pulmonary disease (COPD) and other respiratory phenotypes is not well understood. OBJECTIVES: We investigated causality between eosinophils and: lung function, acute exacerbations of COPD, asthma-COPD overlap (ACO), moderate-to-severe asthma and respiratory infections. METHODS: We performed Mendelian randomisation (MR) using 151 variants from genome-wide association studies of blood eosinophils in UK Biobank/INTERVAL, and respiratory traits in UK Biobank/SpiroMeta, using methods relying on different assumptions for validity. We performed multivariable analyses using eight cell types where there was possible evidence of causation by eosinophils. MEASUREMENTS AND MAIN RESULTS: Causal estimates derived from individual variants were highly heterogeneous, which may arise from pleiotropy. The average effect of raising eosinophils was to increase risk of ACO (weighted median OR per SD eosinophils, 1.44 (95%CI 1.19 to 1.74)), and moderate-severe asthma (weighted median OR 1.50 (95%CI 1.23 to 1.83)), and to reduce forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and FEV1 (weighted median estimator, SD FEV1/FVC: -0.054 (95% CI -0.078 to -0.029), effect only prominent in individuals with asthma). CONCLUSIONS: Broad consistency across MR methods may suggest causation by eosinophils (although of uncertain magnitude), yet heterogeneity necessitates caution: other important mechanisms may be responsible for the impairment of respiratory health by these eosinophil-raising variants. These results could suggest that anti-IL5 agents (designed to lower eosinophils) may be valuable in treating other respiratory conditions, including people with overlapping features of asthma and COPD.

Childhood asthma diagnoses declined during the COVID-19 pandemic in the United States.

BACKGROUND: Prior studies have documented declines in pediatric asthma exacerbations and asthma-related health care utilization during the COVID-19 pandemic, but less is known about the incidence of asthma during the pandemic. METHODS: We conducted a retrospective cohort study of children under age 18 without a prior diagnosis of asthma within a large US commercial claims database. Incident asthma was defined using a combination of diagnosis codes, location of services, and medication dispensing. Crude quarterly rates of asthma diagnosis per 1000 children were calculated, and the incidence rate ratio and 95% confidence interval were estimated for newly diagnosed asthma during versus before the pandemic using negative binomial regression, adjusted for age, sex, region, and season. RESULTS: Compared with 3 years prior to the pandemic, crude incident diagnosis rates of asthma decreased by 52% across the first four quarters of the US pandemic. The covariate-adjusted pandemic-associated incidence rate ratio was 0.47 (95% confidence interval 0.43, 0.51). CONCLUSIONS: New diagnoses of childhood asthma in the US declined by half during the first year of the pandemic. These findings raise important questions whether pandemic-related changes in infectious or other triggers truly altered the incidence of childhood asthma beyond the well-described disruptions in healthcare access.

Disadvantage in early-life and persistent asthma in adolescents: a UK cohort study.

OBJECTIVE: To determine how early-life risk factors explain socioeconomic inequalities in persistent asthma in adolescence. METHODS: We did a causal mediation analysis using data from 7487 children and young people in the UK Millennium Cohort Study. Persistent asthma was defined as having a diagnosis reported at any two or more time points at 7, 11 or 14 years. The main exposure was maternal education, a measure of early-life socioeconomic circumstances (SECs), used to calculate the relative index of inequality. We assessed how blocks of perinatal (maternal health behaviours, infant characteristics and duration of breastfeeding, measured at 9 months) and environmental risk factors (family housing conditions; potential exposure to infections through childcare type and sibling number, and neighbourhood characteristics, measured at 3 years) mediated the total effect of childhood SECs on persistent asthma risk, calculating the proportion mediated and natural indirect effect (NIE) via blocks of mediators. RESULTS: At age 14 the overall prevalence of persistent asthma was 15%. Children of mothers with lower educational qualifications were more likely to have persistent asthma, with a clear social gradient (degree plus: 12.8% vs no qualifications: 20.3%). The NIE gives the effect of SECs acting only via the mediators and shows a 31% increased odds of persistent asthma when SECs are fixed at the highest level, and mediators at the level which would naturally occur at the lowest SECs versus highest SECs (NIE OR 1.31, 95% CI 1.04 to 1.65). Overall, 58.9% (95% CI 52.9 to 63.7) of the total effect (OR 1.70, 95% CI 1.20 to 2.40) of SECs on risk of persistent asthma in adolescence was mediated by perinatal and environmental characteristics. CONCLUSIONS: Perinatal characteristics and the home environment in early life are more important in explaining socioeconomic inequalities in persistent asthma in British adolescents than more distal environmental exposures outside the home.