Use of oral moist tobacco (snus) in puberty and its association with asthma in the population-based RHINESSA study.

OBJECTIVES: To investigate the association of early snus use initiation (≤15 years of age) with asthma and asthma symptoms. DESIGN: Cross-sectional analysis of a population-based cohort. SETTING: Study centres in Norway, Sweden, Iceland, Denmark and Estonia, from 2016 to 2019. PARTICIPANTS: 9002 male and female participants above 15 years of age of the Respiratory Health in Northern Europe, Spain and Australia study. MAIN OUTCOME MEASURES: Current asthma and asthma symptoms. RESULTS: The median age of study participants was 28 years (range 15-53) and 58% were women. 20% had used snus, 29% men and 14% women. Overall, 26% of males and 14% of females using snus started ≤15 years of age. Early snus use initiation was associated with having three or more asthma symptoms (OR 2.70; 95% CI 1.46 to 5.00) and a higher asthma symptom score (ß-coefficient (ß) 0.35; 95% CI 0.07 to 0.63) in women. These associations were weak in men (OR 1.23; 95% CI 0.78 to 1.94; ß 0.16; 95% CI -0.06 to 0.38, respectively). There was evidence for an association of early snus initiation with current asthma (OR 1.72; 95% CI 0.88 to 3.37 in women; OR 1.31; 95% CI 0.84 to 2.06 in men). A sensitivity analysis among participants without smoking history showed stronger estimates for all three outcomes, in both men and women, statistically significant for three or more asthma symptoms in women (OR 3.28; 95% CI 1.18 to 9.10). Finally, no consistent associations with asthma outcomes were found for starting snus after age 15 years. CONCLUSIONS: Snus initiation in puberty was associated with higher likelihood of asthma and asthma symptoms, with the highest estimates in females and those without smoking history. These results raise concerns about the health adversities of early snus initiation and emphasise the need for public health initiatives to protect young people from this tobacco product.

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.

Sex differences in asthma control, lung function and exacerbations: the ATLANTIS study.

BACKGROUND: Asthma is a heterogeneous disease with a prevalence and severity that differs between male and female patients. QUESTION: What are differences between male and female patients with asthma with regard to asthma control, lung function, inflammation and exacerbations? METHODS: We performed a post hoc analysis in the ATLANTIS (Assessment of Small Airways Involvement in Asthma) study, an observational cohort study including patients with asthma from nine countries with a follow-up of 1 year during which patients were characterised with measures of large and small airway function, questionnaires, inflammation and imaging. We compared differences in baseline characteristics and longitudinal outcomes between male and female patients with asthma. RESULTS: 773 patients were enrolled; 450 (58%) of these were female. At baseline, female patients with asthma were in higher Global Initiative for Asthma (GINA) steps (p=0.042), had higher Asthma Control Questionnaire 6 (F: 0.83; M: 0.66, p<0.001) and higher airway resistance as reflected by uncorrected impulse oscillometry outcomes (ie, R5-R20: F: 0.06; M: 0.04 kPa/L/s, p=0.002). Male patients with asthma had more severe airway obstruction (forced expiratory volume in 1 s/forced vital capacity % predicted: F: 91.95; M: 88.33%, p<0.01) and more frequently had persistent airflow limitation (F: 27%; M: 39%, p<0.001). Blood neutrophils were significantly higher in female patients (p=0.014). With Cox regression analysis, female sex was an independent predictor for exacerbations. INTERPRETATION: We demonstrate that female patients are in higher GINA steps, exhibit worse disease control, experience more exacerbations and demonstrate higher airway resistance compared with male patients. The higher exacerbation risk was independent of GINA step and blood eosinophil level. Male patients, in turn, have a higher prevalence of persistent airflow limitation and more severe airflow obstruction. These findings show sex can affect clinical phenotyping and outcomes in asthma. TRIAL REGISTRATION NUMBER: NCT02123667.

Herpes zoster burden in patients with asthma: real-world incidence, healthcare resource utilisation and cost.

BACKGROUND: Herpes zoster (HZ) is a painful condition caused by reactivation of the varicella-zoster virus. The objectives of this study were to compare HZ incidence in adults with asthma versus adults without asthma and to compare healthcare resource use as well as direct costs in adults with HZ and asthma versus adults with asthma alone in the USA. METHODS: This retrospective longitudinal cohort study included adults aged ≥18 years across the USA. Patients were identified from Optum's deidentified Clinformatics Data Mart Database, an administrative claims database, between 1 October 2015 and 28 February 2020, including commercially insured and Medicare Advantage with part D beneficiaries. Cohorts of patients with and without asthma, and separate cohorts of patients with asthma and HZ and with asthma but not HZ, were identified using International Classification of Diseases 10th Revision, Clinical Modification codes. HZ incidence, healthcare resource use and costs were compared, adjusting for baseline characteristics, between the relevant cohorts using generalised linear models. RESULTS: HZ incidence was higher in patients with asthma (11.59 per 1000 person-years) than patients without asthma (7.16 per 1000 person-years). The adjusted incidence rate ratio (aIRR) for HZ in patients with asthma, compared with patients without asthma, was 1.34 (95% CI 1.32 to 1.37). Over 12 months of follow-up, patients with asthma and HZ had more inpatient stays (aIRR 1.11; 95% CI 1.02 to 1.21), emergency department visits (aIRR 1.26; 95% CI 1.18 to 1.34) and outpatient visits (aIRR 1.19; 95% CI 1.16 to 1.22), and direct healthcare costs that were US dollars ($) 3058 (95% CI $1671 to $4492) higher than patients with asthma without HZ. CONCLUSION: Patients with asthma had a higher incidence of HZ than those without asthma, and among patients with asthma HZ added to their healthcare resource use and costs.

Risk factors for asthma-related hospital and intensive care admissions in children, adolescents and adults: a cohort study using primary and secondary care data.

BACKGROUND: Asthma remains a common cause of hospital admissions across the life course. We estimated the contribution of key risk factors to asthma-related hospital and intensive care unit (ICU) admissions in children, adolescents and adults. METHODS: This was a UK-based cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics Admitted Patient Care) data. Patients were eligible if they were aged 5 years and older and had been diagnosed with asthma. This included 90 989 children aged 5-11 years, 114 927 adolescents aged 12-17 years and 1 179 410 adults aged 18 years or older. The primary outcome was asthma-related hospital admissions from 1 January 2017 to 31 December 2019. The secondary outcome was asthma-related ICU admissions. Incidence rate ratios adjusted for demographic and clinical risk factors were estimated using negative binomial models. Population attributable fraction (PAF) was estimated for modifiable risk factors. RESULTS: Younger age groups, females and those from ethnic minority and lower socioeconomic backgrounds had an increased risk of asthma-related hospital admissions. Increasing medication burden, including excessive use of short-acting bronchodilators, was also strongly associated with the primary outcome. Similar risk factors were observed for asthma-related ICU admissions. The key potentially modifiable or treatable risk factors were smoking in adolescents and adults (PAF 6.8%, 95% CI 0.9% to 12.3% and 4.3%, 95% CI 3.0% to 5.7%, respectively), and obesity (PAF 23.3%, 95% CI 20.5% to 26.1%), depression (11.1%, 95% CI 9.1% to 13.1%), gastro-oesophageal reflux disease (2.3%, 95% CI 1.2% to 3.4%), anxiety (2.0%, 95% CI 0.5% to 3.6%) and chronic rhinosinusitis (0.8%, 95% CI 0.3% to 1.3%) in adults. CONCLUSIONS: There are significant sociodemographic inequalities in the rates of asthma-related hospital and ICU admissions. Treating age-specific modifiable risk factors should be considered an integral part of asthma management, which could potentially reduce the rate of avoidable hospital admissions.

Suboptimal peak inspiratory flow rate: a noticeable risk factor for inhaler concordance in patients with chronic airway diseases.

BACKGROUND: Inhaler concordance and the peak inspiratory flow rate (PIFR) are important determinants of treatment effects in patients with chronic airway diseases. Adequate PIFR is required for driving aerosol medication into the lower respiratory tract. However, the relationship between them has not been discussed previously. This study aimed to describe the characteristics of inhaler concordance and PIFR in Chinese patients with chronic airway diseases and discuss the associated variables and the relationship between them. METHODS: In this single-centre, observational study, a total of 680 patients with chronic airway diseases were enrolled from July 2021 to April 2023. We collected data on the socio-demographic and clinical variables of inhaler concordance using the test of adherence to inhalers (TAI) and PIFR. Multivariate logistic regression was conducted to examine variables related to inhaler concordance and PIFR. RESULTS: A total of 49.4% of patients had low concordance. Patients with chronic obstructive pulmonary disease (COPD) were more concordant than patients with asthma (mean TAI score: 43.60 vs 41.20; p<0.01), while there was no difference in concordance between the asthma-COPD overlap group and the asthma or COPD group. Suboptimal PIFR (adjusted OR, 1.61; 95% CI 1.04 to 2.51) increased the risk of poor concordance among all patients, while triple therapy (adjusted OR, 0.60; 95% CI 0.35 to 0.86) reduced the risk. A total of 54.9% of patients had suboptimal PIFR. Older age, lower educational level, use of dry powder inhalers and lower forced expiratory volume in 1 s % predicted were significantly correlated with insufficient PIFR. Subgroup analysis revealed a greater proportion of patients with insufficient PIFR during exacerbation than during the stable phase (61.7% vs 43.5%, p<0.001). CONCLUSION: Inhaler concordance was low, and suboptimal PIFR was a risk factor for poor concordance among Chinese patients with chronic airway diseases. In addition, current inhalation devices may not be suitable, and PIFR reassessment should be considered for patients with COPD during exacerbation. TRIAL REGISTRATION NUMBER: The study was registered in chictr.org.cn (ChiCTR2100052527) on 31 October 2021.

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

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.

Comorbidities associated with adult asthma: a population-based matched cohort study in Finland.

BACKGROUND: Asthma is a common chronic disease characterised by variable respiratory symptoms and airflow limitation, affecting roughly 4%-10% of the adult population. Adult asthma is associated with higher all-cause mortality compared to individuals without asthma. In this study, we investigate the comorbidities that may affect the management of asthma. METHODS: Total of 1648 adults with asthma and 3310 individuals without asthma aged 30-93 were matched with age, gender and area of residency, and followed from 1 January 1997 to 31 December 2013. Baseline information was collected with questionnaires 1997 and follow-up register data from the national discharge registry Finnish Institute for Health and Welfare. Data included diagnoses from outpatient care and day surgery of specialised health care, and data from inpatient care of specialised and primary health care. We included all main diagnoses that had at minimum 200 events and number of diagnoses based on their common appearance with adult asthma. RESULTS: The mean follow-up time varied between 14.2 and 15.1 years, and age at the time of enrolment was 53.9 years for subjects without asthma and 54.4 years for patients with asthma. Chronic obstructive pulmonary disease was 10 times more common among asthmatics. Risk of acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis and vocal cord dysfunction was fourfold and risk of pneumonia, and chronic rhinosinusitis was 2.5 times more common among asthmatics. Sleep apnoea, gastro-oesophageal reflux disease, diabetes, allergic rhinitis and dysfunctional breathing were twofold and cataract nearly twofold higher in the asthmatic group. Adult asthma was also significantly associated with musculoskeletal diseases, incontinence and bronchiectasis. CONCLUSIONS: The most common and most severe comorbidity of adult asthma in this study was chronic obstructive pulmonary disease. Other common comorbidities of adult asthma include acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, allergic rhinitis, dysfunctional breathing, diabetes, pneumonia, sleep apnoea and gastro-oesophageal reflux disease.

Characteristics, treatment patterns and burden of illness in US patients with asthma newly initiating multiple-inhaler triple therapy.

INTRODUCTION: For patients with asthma who remain symptomatic on medium-dose inhaled corticosteroid/long-acting ß2-agonist, add-on long-acting muscarinic antagonist is a treatment option, which can be administered as multiple-inhaler triple therapy (MITT). A high proportion of patients (61.5%-88.2%) discontinue MITT use within 1 year postinitiation; however, which patients discontinue and their treatment patterns at initiation are unknown. This study aimed to understand the demographic, clinical and treatment-related characteristics of patients with asthma who newly initiated MITT, by discontinuation status. METHODS: This retrospective cohort study used administrative data from IBM Truven MarketScan Commercial Claims and Encounters Database with Medicare supplement between 1 January 2016 and 31 December 2019. Adult patients with asthma who initiated MITT between 1 January 2017 and 31 March 2019 were included and were classified based on their discontinuation status. 'Continuous users' had continuous use of MITT and 'discontinuers' discontinued treatment within the 6-month period postinitiation. Demographics and clinical characteristics, asthma treatment use prior to MITT initiation (12-month baseline period), mode of MITT initiation and complexity of regimen were described. RESULTS: Of 4132 patients (mean age: 49.0 years, 67.9% female), 78.0% (n=3224) were discontinuers; 22.0% (n=908) were continuous users. Demographic and other clinical and treatment-related characteristics during baseline were broadly similar between cohorts. A significantly higher proportion of continuous users versus discontinuers had ≥6 dispensed claims for short-acting ß2-agonist canisters (16.0% vs 12.5%; p=0.006) during baseline and initiated a once-daily MITT regimen (35.2% vs 26.2%; p<0.001). Fewer continuous MITT users used a mix of once-daily and twice-daily regimens than those who discontinued MITT (64.3% vs 72.3%; p<0.001). CONCLUSIONS: Most patients with asthma discontinued MITT within 6 months. Results indicate that patients with a history of uncontrolled, symptomatic asthma and those using less complex triple therapy regimens at initiation are less likely to discontinue MITT than patients with controlled asthma and those using a complex MITT regimen.

Respiratory symptoms, exacerbations and sleep disturbances are more common among participants with asthma and chronic airflow limitation: an epidemiological study in Estonia, Iceland and Sweden.

BACKGROUND: Chronic airflow limitation (CAL) is a hallmark of chronic obstructive pulmonary disease but is also present in some patients with asthma. We investigated respiratory symptoms, sleep and health status of participants with and without CAL with particular emphasis on concurrent asthma using data from adult populations in Iceland, Estonia and Sweden investigated within the Burden of Obstructive Lung Disease study. METHODS: All participants underwent spirometry with measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) before and after bronchodilation. CAL was defined as postbronchodilator FEV1/FVC below the lower limit of normal. IgE-sensitisation and serum concentrations of eosinophil-derived neurotoxin (S-EDN) were assessed in a subsample. The participants were divided into four groups: no self-reported doctor's diagnosed asthma or CAL, asthma without CAL, CAL without asthma and asthma and CAL: χ2 test and analysis of variance were used in bivariable analyses and logistic and linear regression when analysing the independent association between respiratory symptoms, exacerbations, sleep-related symptoms and health status towards CAL, adjusting for centre, age, sex, body mass index, smoking history and educational level. RESULTS: Among the 1918 participants, 190 (9.9%) had asthma without CAL, 127 (6.6%) had CAL without asthma and 50 (2.6%) had CAL with asthma. Having asthma with CAL was associated with symptoms such as wheeze (adjusted OR (aOR) 6.53 (95% CI 3.53 to 12.1), exacerbations (aOR 12.8 (95% CI 6.97 to 23.6), difficulties initiating sleep (aOR 2.82 (95% CI 1.45 to 5.48), nocturnal gastro-oesophageal reflux (aOR 3.98 (95% CI 1.79 to 8.82)) as well as lower physical health status. In these analyses, those with no asthma and no CAL were the reference group. The prevalence of IgE-sensitisation was highest in both asthma groups, which also had higher levels of S-EDN. CONCLUSION: Individuals with self-reported asthma with CAL suffer from a higher burden of respiratory and sleep-related symptoms, higher exacerbation rates and lower health status when compared with participants with asthma alone or CAL alone.

Risk of exacerbation and mortality in asthma: a 10-year retrospective financial database analysis of the Hungarian Health Insurance Fund.

INTRODUCTION: Asthma is the most prevalent obstructive pulmonary disease, with drastically improved treatment options over the past decades. However, there is still a proportion of patients with suboptimal level of asthma control, leading to multiple hospitalisation due to severe acute exacerbation (SAE) and earlier death. In our study, we aimed to assess the risk of SAEs and mortality in patients who suffered an SAE. METHODS: The database of the National Health Insurance Fund was used to retrospectively analyse the data of all asthmatic patients who had been hospitalised for an SAE between 2009 and 2019. We used a competing risk model to analyse the effect of each exacerbation on the risk of further SAEs with age, sex, Charlson index and the number of severe and moderate exacerbations included as covariates. RESULT: Altogether, 9257 asthmatic patients suffered at least one exacerbation leading to hospitalisation during the study time. The majority (75.8%) were women, and the average age was 58.24 years. Most patients had at least one comorbidity. 3492 patients suffered at least one further exacerbation and 1193 patients died of any cause. In the competing risk model, each SAE increased the risk of further exacerbations (HR=2.078-7.026; p<0.0001 for each case) but not death. The risk of SAEs was also increased by age (HR=1.008) female sex (HR=1.102) and with the number of days of the first SAE (HR=1.007). CONCLUSIONS: Even though asthma is generally a well-manageable disease, there still are many patients who suffer SAEs that significantly increase the risk of further similar SAEs.

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.

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.

Adherence to application technique of inhaled corticosteroid in patients with asthma and COVID-19 improves outcomes.

BACKGROUND: Inhaled corticosteroids have been widely reported as a preventive measure against the development of severe forms of COVID-19 not only in patients with asthma. METHODS: In 654 Czech and Slovak patients with asthma who developed COVID-19, we investigated whether the correct use of inhaler containing corticosteroids was associated with a less severe course of COVID-19 and whether this had an impact on the need for hospitalisation, measurable lung functions and quality of life (QoL). RESULTS: Of the studied cohort 51.4% had moderate persistent, 29.9% mild persistent and 7.2% severe persistent asthma. We found a significant adverse effect of poor inhaler adherence on COVID-19 severity (p=0.049). We also observed a lower hospitalisation rate in patients adequately taking the inhaler with OR of 0.83. Vital capacity and forced expiratory lung volume deterioration caused by COVID-19 were significantly reversed, by approximately twofold to threefold, in individuals who inhaled correctly. CONCLUSION: Higher quality of inhalation technique of corticosteroids measured by adherence to an inhaled medication application technique (A-AppIT) score had a significant positive effect on reversal of the vital capacity and forced expiratory lung volume in 1 s worsening (p=0.027 and p<0.0001, respectively) due to COVID-19. Scoring higher in the A-AppIT was also associated with significantly improved QoL. All measured variables concordantly and without exception showed a positive improvement in response to better adherence. We suggest that corticosteroids provide protection against the worsening of lungs in patients with COVID-19 and that correct and easily assessable adherence to corticosteroids with appropriate inhalation technique play an important role in preventing severe form of COVID-19.

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.

Asthma in the Brazilian Unified Health Care System: an epidemiological analysis from 2008 to 2021

ABSTRACT Objective: To analyze the number of hospitalizations, the length of hospital stay, and mortality due to asthma, as well as the costs to the Unified Health Care System in Brazil between 2008 and 2021. Methods: This was a cross-sectional epidemiological study using data from the Information Technology Department of the Brazilian Unified Health Care System. Proportional hospitalization and death rates were estimated per 100,000 population by age, microregion, and year. Results: The number of hospitalizations and deaths due to asthma decreased from 2008 to 2021 (205,392 vs. 55,009 and 822 vs. 327, respectively). In addition, a between-sex difference was observed in asthma-related hospitalizations in 2008, and more men were hospitalized in 2021 (51.8%). Asthma mortality rates were similar for both sexes (50.0% each) in 2008, and a slight increase was observed in women's deaths in 2021 (52.9%). Even so, approximately one death/day and more than 55,000 hospitalizations were observed yearly, with a mean length of hospital stay of three days. Additionally, the Southeast region allocated more financial resources to asthma-related hospitalizations. Conclusions: Our results showed that the number of deaths and hospitalizations due to asthma substantially declined during the study period.

Association between antibiotics and asthma risk among adults aged over 40 years: a nationally representative retrospective cohort study.

INTRODUCTION: Several studies have reported that exposure to antibiotics can lead to asthma during early childhood. However, the association between antibiotic use and risk of asthma in the adult population remains unclear. This study aimed to investigate the association between antibiotic use and asthma in adults. METHODS: We used data from the National Health Insurance Service (NHIS)-Health Screening Cohort, which included participants aged ≥40 years who had health screening examination data in 2005-2006. A total of 248 961 participants with a mean age of 55.43 years were enrolled in this retrospective cohort study. To evaluate antibiotic exposure from the NHIS database for 5 years (2002-2006), cumulative usage and multiclass prescriptions were identified, respectively. During the follow-up period (2007-2019), 42 452 patients were diagnosed with asthma. A multivariate Cox proportional hazard regression model was used to assess the association between antibiotic use and newly diagnosed asthma. RESULTS: Participants with antibiotic use for ≥91 days showed a higher risk of asthma (adjusted HR (aHR) 1.84, 95% CI 1.72 to 1.96) compared with participants who did not use antibiotics (n=38 450), with a duration-dependent association (ptrend<0.001). Furthermore, ≥4 antibiotic class user group had an increased risk of asthma (aHR 1.44, 95% CI 1.39 to 1.49) compared with one class of antibiotic use (n=64 698). Also, one class of antibiotic use had a higher risk of asthma (aHR 1.21, 95% CI 1.17 to 1.26) compared with non-users, and it also showed a duration-dependent relationship in all classes, including 1, 2, 3 and ≥4 class group (ptrend<0.001). The duration-response relationship between antibiotic use and increased risk of asthma remained in our sensitivity analyses with the washout and shifting of the index date. CONCLUSIONS: The duration-response pattern observed in antibiotic use and asthma may suggest the implication of proper antibiotic use and management in adults.