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The Journal of Allergy and Clinical... Jun 2024Recent evidence suggests that insulin resistance affects asthma outcomes; however, the effect of the homeostatic measure of insulin resistance (HOMA-IR) on airway...
BACKGROUND AND AIMS
Recent evidence suggests that insulin resistance affects asthma outcomes; however, the effect of the homeostatic measure of insulin resistance (HOMA-IR) on airway inflammation and asthma exacerbations (AEs) is poorly understood.
OBJECTIVES
To analyze the relationship between HOMA-IR and clinical and inflammatory characteristics in patients with asthma, and the association between HOMA-IR and asthma exacerbations (AEs) in the following year.
METHODS
A prospective cohort study recruited participants with asthma, who were classified into the HOMA-IR group and HOMA-IR group based on the cutoff value of 3.80 for HOMA-IR and were observed within 12 months. We evaluated the clinical and inflammatory features, and a 1-year follow-up was conducted to study the exacerbations. A negative binomial regression model was used to analyze the association between HOMA-IR and AEs.
RESULTS
Compared with the patients in the HOMA-IR group (n = 564), patients in the HOMA-IR group (n = 61) had higher levels of BMI, higher waist circumference and waist/hip ratio, higher triglycerides, lower cholesterol high-density lipoproteins (HDL), more neutrophils in the peripheral blood, and elevated IL-5 levels in the induced sputum. Furthermore, patients in the HOMA-IR group had a significantly increased risk for moderate-to-severe AEs (adjusted incidence rate ratio (aIRR) = 2.26, 95% confidence interval (CI) = [1.38, 3.70]), severe AEs (aIRR = 2.42, 95% CI = [1.26, 4.67]), hospitalization(aIRR = 2.54, 95% CI = [1.20, 5.38]), and emergency visits (aIRR = 3.04, 95% CI = [1.80, 8.53]).
CONCLUSION
HOMA-IR was associated with asthma-related clinical features, and airway inflammation, as well as being an independent risk factor for future AEs. Therefore, insulin resistance may have important implications for managing asthma as a potential treatable trait.
PubMed: 38944198
DOI: 10.1016/j.jaip.2024.06.034 -
Cell Genomics Jun 2024The phenotypic impact of compound heterozygous (CH) variation has not been investigated at the population scale. We phased rare variants (MAF ∼0.001%) in the UK...
The phenotypic impact of compound heterozygous (CH) variation has not been investigated at the population scale. We phased rare variants (MAF ∼0.001%) in the UK Biobank (UKBB) exome-sequencing data to characterize recessive effects in 175,587 individuals across 311 common diseases. A total of 6.5% of individuals carry putatively damaging CH variants, 90% of which are only identifiable upon phasing rare variants (MAF < 0.38%). We identify six recessive gene-trait associations (p < 1.68 × 10) after accounting for relatedness, polygenicity, nearby common variants, and rare variant burden. Of these, just one is discovered when considering homozygosity alone. Using longitudinal health records, we additionally identify and replicate a novel association between bi-allelic variation in ATP2C2 and an earlier age at onset of chronic obstructive pulmonary disease (COPD) (p < 3.58 × 10). Genetic phase contributes to disease risk for gene-trait pairs: ATP2C2-COPD (p = 0.000238), FLG-asthma (p = 0.00205), and USH2A-visual impairment (p = 0.0084). We demonstrate the power of phasing large-scale genetic cohorts to discover phenome-wide consequences of compound heterozygosity.
PubMed: 38944039
DOI: 10.1016/j.xgen.2024.100602 -
International Immunopharmacology Jun 2024Several monoclonal antibodies (MoAbs) targeting specific type 2 immune reactions have been developed as innovative therapeutic approaches for chronic inflammatory airway...
OBJECTIVE
Several monoclonal antibodies (MoAbs) targeting specific type 2 immune reactions have been developed as innovative therapeutic approaches for chronic inflammatory airway diseases, such as chronic sinusitis with nasal polyps (CRSwNP) and asthma. However, the clinical safety of these MoAbs and how to choose them are not clear. Therefore, we aimed to assess the systemic drug- and dose-based safety of MoAbs in chronic airway inflammation using network meta-analysis (NMA).
METHODS
Electronic databases were systematically searched for relevant studies published in English between January 2009 and December 2022. Eligible studies must have clearly reported adverse events (AEs) among the MoAbs' safety data.
RESULTS
1). Regarding serious AEs, mepolizumab was significantly safer than placebo; in terms of permanent treatment discontinuation, reslizumab and dupilumab were significantly safer than benralizumab. 2). Regarding asthma worsening, dupilumab was associated with the best safety profile; was safer than dupilumab/300 mg/q2-4w. 3). In terms of injection-site reactions, dupilumab posed a higher risk than placebo; dupilumab/300 mg/qw posed a higher risk than dupilumab/300 mg/q2w and dupilumab/300 mg/q2-4w; lebrikizumab/250 mg/q4w posed a higher risk than lebrikizumab/37.5 mg/q4w; mepolizumab/100 mg/q4w posed a higher risk than mepolizumab/75 mg/q4w; benralizumab/30 mg/q4-8w posed a higher risk than benralizumab/20 mg/q4-8w. 4) In CRSwNP patients combined with asthma, the risks of experiencing AEs were not increased.
CONCLUSION
Overall, biologics are safe and well tolerated in chronic inflammatory airway disease. This drug- and dose-based NMA provides further evidence on the different safety profiles of different emerging MoAbs. This information may help guide rational drug use and provide clinical recommendations for choosing MoAbs.
TRIAL REGISTRATION
SYSTEMATIC REVIEW REGISTRATION (PROSPERO #CRD42023387610).
PubMed: 38943971
DOI: 10.1016/j.intimp.2024.112462 -
Journal of Psychosomatic Research Jun 2024This cross-sectional study examines the link between chronic diseases and suicidal thoughts in U.S. adults using 2013-2018 National Health and Nutrition Examination...
BACKGROUND
This cross-sectional study examines the link between chronic diseases and suicidal thoughts in U.S. adults using 2013-2018 National Health and Nutrition Examination Survey (NHANES) data, aiming to identify potential risk factors for suicidal ideation.
METHODS
Using NHANES data, we analyzed the association between various chronic conditions (hypertension, diabetes, asthma, etc.) and suicidal thoughts, employing logistic regression models adjusted for demographics and lifestyle factors.
RESULTS
The analysis of 8891 participants revealed a significant association between suicidal thoughts and chronic diseases such as liver disease, diabetes, and asthma. The risk of suicidal ideation is higher with the number of chronic conditions.
CONCLUSION
Our findings suggest a strong link between the presence and number of chronic diseases and the risk of suicidal thoughts, emphasizing the importance of integrated care approaches that address both physical and mental health needs.
PubMed: 38943724
DOI: 10.1016/j.jpsychores.2024.111854 -
Helicobacter 2024The "hygiene hypothesis" states that reduced exposure to microbial antigens due to an excessively hygienic environment can increase the risk of developing autoimmune...
BACKGROUND
The "hygiene hypothesis" states that reduced exposure to microbial antigens due to an excessively hygienic environment can increase the risk of developing autoimmune diseases, including atopic disorders and asthma. In recent decades, there has been a progressive decline in the prevalence of numerous microorganisms following improved hygienic-sanitary conditions. More specifically, several studies reported an inverse association between the reduction in Helicobacter pylori infection and the rise of asthma and allergic disorders.
AIM
To evaluate the prevalence of atopic disorders in a pediatric population in relation to seropositivity against H. pylori.
METHODS
Children from Northern Sardinia, Italy, referred to the local Children's Hospital for any reason, were investigated to identify risk factors, especially H. pylori infection, associated with atopic disorders. A validated questionnaire, including demographics, house size, history of breastfeeding, residence, school or daycare center attendance, exposure to animals, and a defined diagnosis of atopy-including asthma-was filled out by a trained pediatrician according to parents' answers and child records. A blood sample was collected from each participant and immunoglobulin G against H. pylori was assessed by a locally validated ELISA test.
RESULTS
The seroprevalence of H. pylori infection was 11.7% among 492 children (240 females). Thirty-two children had a confirmed diagnosis of asthma and 12 of allergy. No one child showed both conditions. Statistically significant differences in H. pylori seropositivity were not detected between children with or without atopy (8.4% vs. 12.6; p = 0.233). Although atopic disorders were more frequent in children exposed to traditional atopic risk factors, none of them showed to be significant after adjusting for all covariates.
CONCLUSIONS
Serologically assessed H. pylori infection was not significantly associated with a reduced risk of atopic diseases in children.
Topics: Humans; Italy; Helicobacter Infections; Female; Male; Child; Helicobacter pylori; Child, Preschool; Hypersensitivity; Adolescent; Prevalence; Seroepidemiologic Studies; Antibodies, Bacterial; Cohort Studies; Risk Factors; Infant; Surveys and Questionnaires; Immunoglobulin G; Asthma
PubMed: 38943311
DOI: 10.1111/hel.13107 -
BMC Infectious Diseases Jun 2024Most evidence of the waning of vaccine effectiveness is limited to a relatively short period after vaccination.
BACKGROUND
Most evidence of the waning of vaccine effectiveness is limited to a relatively short period after vaccination.
METHODS
Data obtained from a linked database of healthcare administrative claims and vaccination records maintained by the municipality of a city in the Kanto region of Japan were used in this study. The study period extended from April 1, 2020, to December 31, 2022. The duration of the effectiveness of the COVID-19 vaccine was analyzed using a time-dependent piecewise Cox proportional hazard model using the age, sex and history of cancer, diabetes, chronic obstructive pulmonary disease, asthma, chronic kidney disease, and cardiovascular disease as covariates.
RESULTS
Among the 174,757 eligible individuals, 14,416 (8.3%) were diagnosed with COVID-19 and 936 (0.54%) were hospitalized for COVID-19. Multivariate analysis based on the time-dependent Cox regression model with reference of non-vaccine group revealed a lower incidence of COVID-19 in the one-dose group (hazard ratio, 0.76 [95% confidence interval, 0.63-0.91]), two-dose (0.89 [0.85-0.93]), three-dose (0.80 [0.76-0.85]), four-dose (0.93 [0.88-1.00]), and five-dose (0.72 [0.62-0.84]) groups. A lower incidence of COVID-19-related hospitalization was observed in the one-dose group (0.42 [0.21-0.81]), two-dose (0.44 [0.35-0.56]), three-dose (0.38 [0.30-0.47]), four-dose (0.20 [0.14-0.28]), and five-dose (0.11 [0.014-0.86]) groups. Multivariable analyses based on the time-dependent piecewise Cox proportional hazard model with reference of non-vaccine group revealed significant preventive effects of the vaccine for 4 months for the incidence of COVID-19 and ≥ 6 months for hospitalization.
CONCLUSIONS
Vaccine effectiveness showed gradual attenuation with time after vaccination; however, protective effects against the incidence of COVID-19 and hospitalization were maintained for 4 months and ≥ 6 months, respectively. These results may aid in formulating routine vaccination plans after the COVID-19 pandemic.
Topics: Humans; COVID-19; Japan; Female; Male; COVID-19 Vaccines; Middle Aged; Retrospective Studies; Aged; Adult; Registries; SARS-CoV-2; Vaccine Efficacy; Hospitalization; Proportional Hazards Models; Vaccination; Young Adult; Aged, 80 and over; Incidence; Time Factors
PubMed: 38943060
DOI: 10.1186/s12879-024-09488-6 -
Physiological Reports Jul 2024Supplemental O (hyperoxia) is a critical intervention for premature infants (<34 weeks) but consequently is associated with development of bronchial airway...
Supplemental O (hyperoxia) is a critical intervention for premature infants (<34 weeks) but consequently is associated with development of bronchial airway hyperreactivity (AHR) and asthma. Clinical practice shifted toward the use of moderate hyperoxia (<60% O), but risk for subsequent airway disease remains. In mouse models of moderate hyperoxia, neonatal mice have increased AHR with effects on airway smooth muscle (ASM), a cell type involved in airway tone, bronchodilation, and remodeling. Understanding mechanisms by which moderate O during the perinatal period initiates sustained airway changes is critical to drive therapeutic advancements toward treating airway diseases. We propose that cellular clock factor BMAL1 is functionally important in developing mouse airways. In adult mice, cellular clocks target pathways highly relevant to asthma pathophysiology and Bmal1 deletion increases inflammatory response, worsens lung function, and impacts survival outcomes. Our understanding of BMAL1 in the developing lung is limited, but our previous findings show functional relevance of clocks in human fetal ASM exposed to O. Here, we characterize Bmal1 in our established mouse neonatal hyperoxia model. Our data show that Bmal1 KO deleteriously impacts the developing lung in the context of O and these data highlight the importance of neonatal sex in understanding airway disease.
Topics: Animals; Hyperoxia; ARNTL Transcription Factors; Mice; Female; Animals, Newborn; Male; Lung; Mice, Inbred C57BL; Mice, Knockout; Sex Characteristics
PubMed: 38942729
DOI: 10.14814/phy2.16122 -
The Lancet. Public Health Jul 2024The COVID-19 pandemic disrupted health-care delivery, including difficulty accessing in-person care, which could have increased the need for strong pharmacological pain...
BACKGROUND
The COVID-19 pandemic disrupted health-care delivery, including difficulty accessing in-person care, which could have increased the need for strong pharmacological pain relief. Due to the risks associated with overprescribing of opioids, especially to vulnerable populations, we aimed to quantify changes to measures during the COVID-19 pandemic, overall, and by key subgroups.
METHODS
For this interrupted time-series analysis study conducted in England, with National Health Service England approval, we used routine clinical data from more than 20 million general practice adult patients in OpenSAFELY-TPP, which is a a secure software platform for analysis of electronic health records. We included all adults registered with a primary care practice using TPP-SystmOne software. Using interrupted time-series analysis, we quantified prevalent and new opioid prescribing before the COVID-19 pandemic (January, 2018-February, 2020), during the lockdown (March, 2020-March, 2021), and recovery periods (April, 2021-June, 2022), overall and stratified by demographics (age, sex, deprivation, ethnicity, and geographical region) and in people in care homes identified via an address-matching algorithm.
FINDINGS
There was little change in prevalent prescribing during the pandemic, except for a temporary increase in March, 2020. We observed a 9·8% (95% CI -14·5 to -6·5) reduction in new opioid prescribing from March, 2020, with a levelling of the downward trend, and rebounding slightly after April, 2021 (4·1%, 95% CI -0·9 to 9·4). Opioid prescribing rates varied by demographics, but we found a reduction in new prescribing for all subgroups except people aged 80 years or older. Among care home residents, in April, 2020, parenteral opioid prescribing increased by 186·3% (153·1 to 223·9).
INTERPRETATION
Opioid prescribing increased temporarily among older people and care home residents, likely reflecting use to treat end-of-life COVID-19 symptoms. Despite vulnerable populations being more affected by health-care disruptions, disparities in opioid prescribing by most demographic subgroups did not widen during the pandemic. Further research is needed to understand what is driving the changes in new opioid prescribing and its relation to changes to health-care provision during the pandemic.
FUNDING
The Wellcome Trust, Medical Research Council, The National Institute for Health and Care Research, UK Research and Innovation, and Health Data Research UK.
Topics: Humans; England; COVID-19; Interrupted Time Series Analysis; Analgesics, Opioid; Male; Female; Middle Aged; Aged; Adult; Practice Patterns, Physicians'; Drug Prescriptions; Young Adult; Cohort Studies; Adolescent; Aged, 80 and over; Pandemics
PubMed: 38942555
DOI: 10.1016/S2468-2667(24)00100-2 -
Korean Journal of Radiology Jul 2024To evaluate the role of visual and quantitative chest CT parameters in assessing treatment response in patients with severe asthma.
OBJECTIVE
To evaluate the role of visual and quantitative chest CT parameters in assessing treatment response in patients with severe asthma.
MATERIALS AND METHODS
Korean participants enrolled in a prospective multicenter study, named the Precision Medicine Intervention in Severe Asthma study, from May 2020 to August 2021, underwent baseline and follow-up chest CT scans (inspiration/expiration) 10-12 months apart, before and after biologic treatment. Two radiologists scored bronchiectasis severity and mucus plugging extent. Quantitative parameters were obtained from each CT scan as follows: normal lung area (normal), air trapping without emphysema (AT without emph), air trapping with emphysema (AT with emph), and airway (total branch count, Pi10). Clinical parameters, including pulmonary function tests (forced expiratory volume in 1 s [FEV1] and FEV1/forced vital capacity [FVC]), sputum and blood eosinophil count, were assessed at initial and follow-up stages. Changes in CT parameters were correlated with changes in clinical parameters using Pearson or Spearman correlation.
RESULTS
Thirty-four participants (female:male, 20:14; median age, 50.5 years) diagnosed with severe asthma from three centers were included. Changes in the bronchiectasis and mucus plugging extent scores were negatively correlated with changes in FEV1 and FEV1/FVC (ρ = from -0.544 to -0.368, all < 0.05). Changes in quantitative CT parameters were correlated with changes in FEV1 (normal, = 0.373 [ = 0.030], AT without emph, = -0.351 [ = 0.042]), FEV1/FVC (normal, = 0.390 [ = 0.022], AT without emph, = -0.370 [ = 0.031]). Changes in total branch count were positively correlated with changes in FEV1 ( = 0.349 [ = 0.043]). There was no correlation between changes in Pi10 and the clinical parameters ( > 0.05).
CONCLUSION
Visual and quantitative CT parameters of normal, AT without emph, and total branch count may be effective for evaluating treatment response in patients with severe asthma.
Topics: Humans; Male; Female; Asthma; Middle Aged; Tomography, X-Ray Computed; Prospective Studies; Severity of Illness Index; Adult; Treatment Outcome; Respiratory Function Tests; Aged
PubMed: 38942461
DOI: 10.3348/kjr.2024.0110 -
Annals of Allergy, Asthma & Immunology... Jun 2024Asthma is a prevalent health concern among Illinois children and management is significantly influenced by social determinants. Seventeen states have adopted stock...
BACKGROUND
Asthma is a prevalent health concern among Illinois children and management is significantly influenced by social determinants. Seventeen states have adopted stock inhaler laws, but implementation varies widely.
OBJECTIVE
To assess critical barriers to implementation and address sustainability of stock inhaler programming in school-based asthma care in IL.
METHODS
Semi-structured interviews were conducted with high asthma burden school districts in IL to assess barriers in implementing stock inhaler policies and resultant programming. Thematic analysis was performed, using Atlas.ti to identify and code "threats" to future sustainability. Data was synthesized and presented to stakeholders for barrier mitigation. A schematic flow chart outlining steps to support sustainability was created.
RESULTS
Eighteen interviews were conducted with key community partners across eight Illinois school districts, representing rural, urban, and suburban areas. Analysis revealed 25 barriers, with several identified as "threats" to future sustainability, including liability concerns, follow-up care assurance, funding/resources, pharmacy dispensing practices, district-level readiness to change, and nurse staffing. Stakeholders formed a statewide coalition to address these barriers, increase awareness, plan evaluations, and advise on state funding allocation. A national stock inhaler toolkit tailored to school administrative needs was developed to support sustainability efforts.
CONCLUSION
Strategic stakeholder and community engagement are vital for establishing and sustaining stock inhaler programs that adhere to policy mandates. Many districts face challenges initiating and maintaining such programs without critical barrier mitigation and support. Collaborative solutions are necessary to ensure effective school-based asthma management and mitigate persistent pediatric asthma health disparities.
PubMed: 38942380
DOI: 10.1016/j.anai.2024.06.023