Immune Response Dynamics and Biomarkers in COVID-19 Patients.

BACKGROUND: The immune response dynamics in COVID-19 patients remain a subject of intense investigation due to their implications for disease severity and treatment outcomes. We examined changes in leukocyte levels, eosinophil activity, and cytokine profiles in patients hospitalized with COVID-19. METHODS: Serum samples were collected within the first 10 days of hospitalization/confirmed infection and analyzed for eosinophil granule proteins (EGP) and cytokines. Information from medical records including comorbidities, clinical symptoms, medications, and complete blood counts were collected at the time of admission, during hospitalization and at follow up approximately 3 months later. RESULTS: Serum levels of eotaxin, type 1 and type 2 cytokines, and alarmin cytokines were elevated in COVID-19 patients, highlighting the heightened immune response (p < 0.05). However, COVID-19 patients exhibited lower levels of eosinophils and eosinophil degranulation products compared to hospitalized controls (p < 0.05). Leukocyte counts increased consistently from admission to follow-up, indicative of recovery. CONCLUSION: Attenuated eosinophil activity alongside elevated chemokine and cytokine levels during active infection, highlights the complex interplay of immune mediators in the pathogenesis COVID-19 and underscores the need for further investigation into immune biomarkers and treatment strategies.

Three-dimensional MR Neurography of the Brachial Plexus: Vascular Suppression with Low-dose Ferumoxytol.

Background The efficacy of ferumoxytol, an ultrasmall superparamagnetic iron oxide particle for three-dimensional (3D) MR neurography, has yet to be evaluated. Purpose To evaluate the effects of low-dose ferumoxytol for vascular suppression and nerve visualization in 3D brachial plexus MR neurography as a pilot study. Materials and Methods Volunteers without anemia were prospectively enrolled in July 2021. Brachial plexus MR neurography was performed 30 minutes following infusion of 25% of the standard (510 mg of iron) therapeutic ferumoxytol dose with use of a 3D short-tau inversion recovery T2-weighted fast spin-echo sequence. The 3D fast spin-echo was acquired with and without the use of additional flow suppression techniques. Two musculoskeletal radiologists qualitatively evaluated examinations for the degree of vascular suppression (0-3, none to complete), nerve visualization (0-2, none to full), and motion artifact (0-4, none to severe). Nerve-to-fat, muscle, or vessel contrast ratios were calculated with use of manually drawn regions of interests. Comparisons of the proportion of scans with adequate image quality (vascular suppression, 3; nerve visualization, 1, 2; motion artifacts, 0, 1) were made with use of the McNemar test. Comparisons of quantitative contrast ratios were performed with use of Wilcoxon signed rank tests. P < .05 was deemed statistically significant. Results There were 12 volunteers (mean age, 25 years ± 3; six women) evaluated. The scans with adequate vascular suppression increased from 0% to 98% with and without ferumoxytol, respectively (P < .001). All individual nerve assessments of adequate nerve visualization increased from 4%-63% to 36%-100% without and with ferumoxytol, respectively (P < .001-.010), while motion artifacts were unchanged (from 33% to 52%, P = .212). Quantitatively, nerve-to-vessel contrast ratios increased from 0.6 without to 7.6 with ferumoxytol (P < .001). The addition of flow suppression did not change nerve-to-vessel contrast ratio quantitatively (from 7.5 to 8.4, P > .99) following ferumoxytol. Conclusion Low-dose ferumoxytol improved vascular suppression and nerve visualization in three-dimensional MR neurography of the brachial plexus compared to imaging without ferumoxytol. © RSNA, 2022.

Regional differences in the contribution of smoking, dietary and cooking behaviours to airflow obstruction in China: A population-based case-control study.

BACKGROUND AND OBJECTIVE: The major contributing risk factors to airflow obstruction (AO) in China remain largely unknown. We examined the environmental and lifestyle risk factors of unrecognized AO in the baseline of a population-based cohort drawn from 115 urban and rural communities across 12 provinces in China. METHODS: Amongst 46,285 adults recruited from 2005 to 2009, 3686 were identified with AO on spirometry (defined by the ratio of forced expiratory volume in the first second to forced vital capacity <0.7) and without known chronic lung disease. These cases were age- and sex-matched to 11,129 controls with normal spirometry and no chronic lung disease from the same community. Conditional multivariable adjusted OR and population attributable fraction (PAF) were calculated for each identified risk factor and their combined effect. RESULTS: Compared to controls, smoking initiation age <20 years (OR 1.22 [95% CI 1.01-1.48]), smoking duration ≥40 years (OR 1.82 [1.50-2.22]), low vegetables (OR 1.86 [1.67-2.07]) and fruits (OR 1.14 [1.02-1.29]) intake, cooking with biomass fuels (OR 2.54 [2.32-2.78]) and poor kitchen ventilation (OR 1.37 [1.19-1.58]) were significantly associated with elevated risks of unrecognized AO. The combined effect of these lifestyle factors significantly elevated the odds by 25 fold (18.6-34.3). The addition of prior tuberculosis and low socioeconomic status further increased the odds to 40.1 (28.2-57.0) and the PAF to 66.7% (51.1-78.1). CONCLUSION: Smoking, unhealthy diet, biomass cooking fuels and low socioeconomic status are strongly associated with AO. Addressing these risk factors could substantially reduce the burden of AO in China.

Associations between lung function and physical and cognitive health in the Canadian Longitudinal Study on Aging (CLSA): A cross-sectional study from a multicenter national cohort.

BACKGROUND: Low lung function is associated with high mortality and adverse cardiopulmonary outcomes. Less is known of its association with broader health indices such as self-reported respiratory symptoms, perceived general health, and cognitive and physical performance. The present study seeks to address the association between forced expiratory volume in 1 second (FEV1), an indicator of lung function, with broad markers of general health, relevant to aging trajectory in the general population. METHODS AND FINDINGS: From the Canadian general population, 22,822 adults (58% females, mean age 58.8 years [standard deviation (SD) 9.6]) were enrolled from the community between June 2012 and April 2015 from 11 Canadian cities and 7 provinces. Mixed effects regression was used to assess the cross-sectional relationship between FEV1 with self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance. All associations were adjusted for age, sex, body mass index (BMI), education, smoking status, and self-reported comorbidities and expressed as adjusted odds ratios (aORs). Based on the Global Lung Function Initiative (GLI) reference values, 38% (n = 8,626) had normal FEV1 (z-scores >0), 37% (n = 8,514) mild (z-score 0 to > -1 SD), 19% (n = 4,353) moderate (z-score -1 to > -2 SD), and 6% (n = 1,329) severely low FEV1 (z-score = < -2 SD). There was a graded association between lower FEV1 with higher aOR [95% CI] of self-reported moderate to severe respiratory symptoms (mild FEV1 1.09 [0.99 to 1.20] p = 0.08, moderate 1.45 [1.28 to 1.63] p < 0.001, and severe 2.67 [2.21 to 3.23] p < 0.001]), perceived poor health (mild 1.07 [0.9 to 1.27] p = 0.45, moderate 1.48 [1.24 to 1.78] p = <0.001, and severe 1.82 [1.42 to 2.33] p < 0.001]), and impaired cognitive performance (mild 1.03 [0.95 to 1.12] p = 0.41, moderate 1.16 [1.04 to 1.28] p < 0.001, and severe 1.40 [1.19 to 1.64] p < 0.001]). Similar graded association was observed between lower FEV1 with lower physical performance on gait speed, Timed Up and Go (TUG) test, standing balance, and handgrip strength. These associations were consistent across different strata by age, sex, tobacco smoking, obstructive, and nonobstructive impairment on spirometry. A limitation of the current study is the observational nature of these findings and that causality cannot be inferred. CONCLUSIONS: We observed graded associations between lower FEV1 with higher odds of disabling respiratory symptoms, perceived poor general health, and lower cognitive and physical performance. These findings support the broader implications of measured lung function on general health and aging trajectory.

Adverse health impacts of cooking with kerosene: A multi-country analysis within the Prospective Urban and Rural Epidemiology Study.

BACKGROUND: Kerosene, which was until recently considered a relatively clean household fuel, is still widely used in low- and middle-income countries for cooking and lighting. However, there is little data on its health effects. We examined cardiorespiratory effects and mortality in households using kerosene as their primary cooking fuel within the Prospective Urban Rural Epidemiology (PURE) study. METHODS: We analyzed baseline and follow-up data on 31,490 individuals from 154 communities in China, India, South Africa, and Tanzania where there was at least 10% kerosene use for cooking at baseline. Baseline comorbidities and health outcomes during follow-up (median 9.4 years) were compared between households with kerosene versus clean (gas or electricity) or solid fuel (biomass and coal) use for cooking. Multi-level marginal regression models adjusted for individual, household, and community level covariates. RESULTS: Higher rates of prevalent respiratory symptoms (e.g. 34% [95% CI:15-57%] more dyspnea with usual activity, 44% [95% CI: 21-72%] more chronic cough or sputum) and lower lung function (differences in FEV1: -46.3 ml (95% CI: -80.5; -12.1) and FVC: -54.7 ml (95% CI: -93.6; -15.8)) were observed at baseline for kerosene compared to clean fuel users. The odds of hypertension was slightly elevated but no associations were observed for blood pressure. Prospectively, kerosene was associated with elevated risks of all-cause (HR: 1.32 (95% CI: 1.14-1.53)) and cardiovascular (HR: 1.34 (95% CI: 1.00-1.80)) mortality, as well as major fatal and incident non-fatal cardiovascular (HR: 1.34 (95% CI: 1.08-1.66)) and respiratory (HR: 1.55 (95% CI: 0.98-2.43)) diseases, compared to clean fuel use. Further, compared to solid fuel users, those using kerosene had 20-47% higher risks for the above outcomes. CONCLUSIONS: Kerosene use for cooking was associated with higher rates of baseline respiratory morbidity and increased risk of mortality and cardiorespiratory outcomes during follow-up when compared to either clean or solid fuels. Replacing kerosene with cleaner-burning fuels for cooking is recommended.

Regulated Expansion and Survival of Chimeric Antigen Receptor-Modified T Cells Using Small Molecule-Dependent Inducible MyD88/CD40.

Anti-tumor efficacy of T cells engineered to express chimeric antigen receptors (CARs) is dependent on their specificity, survival, and in vivo expansion following adoptive transfer. Toll-like receptor (TLR) and CD40 signaling in T cells can improve persistence and drive proliferation of antigen-specific CD4+ and CD8+ T cells following pathogen challenge or in graft-versus-host disease (GvHD) settings, suggesting that these costimulatory pathways may be co-opted to improve CAR-T cell persistence and function. Here, we present a novel strategy to activate TLR and CD40 signaling in human T cells using inducible MyD88/CD40 (iMC), which can be triggered in vivo via the synthetic dimerizing ligand, rimiducid, to provide potent costimulation to CAR-modified T cells. Importantly, the concurrent activation of iMC (with rimiducid) and CAR (by antigen recognition) is required for interleukin (IL)-2 production and robust CAR-T cell expansion and may provide a user-controlled mechanism to amplify CAR-T cell levels in vivo and augment anti-tumor efficacy.

Ingesting A Sports Drink Enhances Simulated Ice Hockey Performance While Reducing Perceived Effort.

This study determined whether ingesting a carbohydrate-electrolyte solution (CES) vs. progressive dehydration affected skeletal muscle glycogen use and performance in ice hockey players during simulated ice hockey exercise comprised of 3 active "periods". Seven males (21.3±0.3 years, 184.7±1.2 cm, 84.2±3.9 kg, and 49.6±1.8 mL·kg-1·min-1) performed a hockey-specific protocol on two occasions and either dehydrated progressively (NF), or stayed well-hydrated by ingesting a CES. Muscle biopsies were taken at rest, before the 3rd period (P3), and after the final sprint in the protocol. Compared to dehydration in the NF trial (-1.8% BM), CES ingestion enhanced voluntary performance (151.0±8.0 vs. 144.1±8.7 kJ) and glycogen use (177.5±31.1 vs. 103.5±16.2 mmol·kg dm-1), and reduced perceived exertion (16±1 vs. 18±1) in P3. Mean core temperature was reduced by CES ingestion throughout the protocol (38.0±0.2 vs. 38.1±0.1°C). These results suggest that compared to progressive dehydration, staying hydrated by ingesting a CES helps preserve performance, while reducing thermal and perceptual strains, in P3 of cycle-based simulation of ice hockey exercise. These benefits are observed despite greater glycogen use in P3 with CES ingestion.

Mild Dehydration Does Not Influence Performance Or Skeletal Muscle Metabolism During Simulated Ice Hockey Exercise In Men.

This study determined whether mild dehydration influenced skeletal muscle glycogen use, core temperature or performance during high-intensity, intermittent cycle-based exercise in ice hockey players vs. staying hydrated with water. Eight males (21.6 ± 0.4 yr, 183.5 ± 1.6 cm, 83.9 ± 3.7 kg, 50.2 ± 1.9 ml·kg-1·min-1) performed two trials separated by 7 days. The protocol consisted of 3 periods (P) containing 10 × 45-s cycling bouts at ~133% VO2max, followed by 135 s of passive rest. Subjects drank no fluid and dehydrated during the protocol (NF), or maintained body mass by drinking WATER. Muscle biopsies were taken at rest, immediately before and after P3. Subjects were mildly dehydrated (-1.8% BM) at the end of P3 in the NF trial. There were no differences between the NF and WATER trials for glycogen use (P1+P2; 350.1 ± 31.9 vs. 413.2 ± 33.2, P3; 103.5 ± 16.2 vs. 131.5 ± 18.9 mmol·kg dm-1), core temperature (P1; 37.8 ± 0.1 vs. 37.7 ± 0.1, P2; 38.2 ± 0.1 vs. 38.1 ± 0.1, P3; 38.3 ± 0.1 vs. 38.2 ± 0.1 °C) or performance (P1; 156.3 ± 7.8 vs. 154.4 ± 8.2, P2; 150.5 ± 7.8 vs. 152.4 ± 8.3, P3; 144.1 ± 8.7 vs. 148.4 ± 8.7 kJ). This study demonstrated that typical dehydration experienced by ice hockey players (~1.8% BM loss), did not affect glycogen use, core temperature, or voluntary performance vs. staying hydrated by ingesting water during a cycle-based simulation of ice hockey exercise in a laboratory environment.

LMW-E/CDK2 deregulates acinar morphogenesis, induces tumorigenesis, and associates with the activated b-Raf-ERK1/2-mTOR pathway in breast cancer patients.

Elastase-mediated cleavage of cyclin E generates low molecular weight cyclin E (LMW-E) isoforms exhibiting enhanced CDK2-associated kinase activity and resistance to inhibition by CDK inhibitors p21 and p27. Approximately 27% of breast cancers express high LMW-E protein levels, which significantly correlates with poor survival. The objective of this study was to identify the signaling pathway(s) deregulated by LMW-E expression in breast cancer patients and to identify pharmaceutical agents to effectively target this pathway. Ectopic LMW-E expression in nontumorigenic human mammary epithelial cells (hMECs) was sufficient to generate xenografts with greater tumorigenic potential than full-length cyclin E, and the tumorigenicity was augmented by in vivo passaging. However, cyclin E mutants unable to interact with CDK2 protected hMECs from tumor development. When hMECs were cultured on Matrigel, LMW-E mediated aberrant acinar morphogenesis, including enlargement of acinar structures and formation of multi-acinar complexes, as denoted by reduced BIM and elevated Ki67 expression. Similarly, inducible expression of LMW-E in transgenic mice generated hyper-proliferative terminal end buds resulting in enhanced mammary tumor development. Reverse-phase protein array assay of 276 breast tumor patient samples and cells cultured on monolayer and in three-dimensional Matrigel demonstrated that, in terms of protein expression profile, hMECs cultured in Matrigel more closely resembled patient tissues than did cells cultured on monolayer. Additionally, the b-Raf-ERK1/2-mTOR pathway was activated in LMW-E-expressing patient samples, and activation of this pathway was associated with poor disease-specific survival. Combination treatment using roscovitine (CDK inhibitor) plus either rapamycin (mTOR inhibitor) or sorafenib (a pan kinase inhibitor targeting b-Raf) effectively prevented aberrant acinar formation in LMW-E-expressing cells by inducing G1/S cell cycle arrest. LMW-E requires CDK2-associated kinase activity to induce mammary tumor formation by disrupting acinar development. The b-Raf-ERK1/2-mTOR signaling pathway is aberrantly activated in breast cancer and can be suppressed by combination treatment with roscovitine plus either rapamycin or sorafenib.

Long-Term Functional Limitations and Predictors of Recovery after COVID-19: A Multicenter Prospective Cohort Study.

BACKGROUND: Limited data exist on post-severe COVID-19 functional trajectory, particularly considering premorbid status. We characterized 1-year functional recovery post-hospitalization for COVID-19, highlighting predictors of long-term recovery. METHODS: We enrolled adult patients with lab-confirmed SARS-CoV-2 infection and hospitalized for COVID-19 sequelae, from five major Ontario, Canada hospitals in a prospective cohort study. Assessments included telephone interviews on admission followed by telephone and in-person assessments at 3-, 6-, 9-, and 12-months post-discharge. The Activity-Measure for Post-Acute Care (AM-PAC) Mobility and Cognition scales were administered at baseline and every 3 months for 1 year. Secondary outcomes included symptoms, spirometry, physical performance, dyspnea, fatigue, distress, anxiety and depression, and quality of life. RESULTS: 254 patients (57.1% male) with a mean age of 60.0 (±13.1) years and an average hospital stay of 14.3 (±19.7) days agreed to participate. At 12 months, 55.3% demonstrated clinically important deficits in mobility and 38.8% had cognitive deficits compared to premorbid levels. Fatigue was reported in 44.2%, followed by difficulty walking long distances in 35.8% and dyspnea in 33.0%. Almost 40% of patients had an FEV1(% Pred) < 80% at 12 months, 60.3% had impairments in physical performance, and 44.5% had problems with anxiety or depression. Predictors of better mobility at 12 months included higher premorbid mobility status, male sex, shorter hospital stay, fewer comorbidities, and higher FEV1 (% pred) at the 3-month follow-up. CONCLUSIONS: Our study provides compelling evidence of the long-term impact of COVID-19 on functional and cognitive status 1-year post-infection.

Machine learning enabled detection of COVID-19 pneumonia using exhaled breath analysis: a proof-of-concept study.

Detection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) relies on real-time-reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. The false-negative rate of RT-PCR can be high when viral burden and infection is localized distally in the lower airways and lung parenchyma. An alternate safe, simple and accessible method for sampling the lower airways is needed to aid in the early and rapid diagnosis of COVID-19 pneumonia. In a prospective unblinded observational study, patients admitted with a positive RT-PCR and symptoms of SARS-CoV-2 infection were enrolled from three hospitals in Ontario, Canada. Healthy individuals or hospitalized patients with negative RT-PCR and without respiratory symptoms were enrolled into the control group. Breath samples were collected and analyzed by laser absorption spectroscopy (LAS) for volatile organic compounds (VOCs) and classified by machine learning (ML) approaches to identify unique LAS-spectra patterns (breathprints) for SARS-CoV-2. Of the 135 patients enrolled, 115 patients provided analyzable breath samples. Using LAS-breathprints to train ML classifier models resulted in an accuracy of 72.2%-81.7% in differentiating between SARS-CoV2 positive and negative groups. The performance was consistent across subgroups of different age, sex, body mass index, SARS-CoV-2 variants, time of disease onset and oxygen requirement. The overall performance was higher than compared to VOC-trained classifier model, which had an accuracy of 63%-74.7%. This study demonstrates that a ML-based breathprint model using LAS analysis of exhaled breath may be a valuable non-invasive method for studying the lower airways and detecting SARS-CoV-2 and other respiratory pathogens. The technology and the ML approach can be easily deployed in any setting with minimal training. This will greatly improve access and scalability to meet surge capacity; allow early and rapid detection to inform therapy; and offers great versatility in developing new classifier models quickly for future outbreaks.

Risk factors for recognized and unrecognized SARS-CoV-2 infection: a seroepidemiologic analysis of the Prospective Urban Rural Epidemiology (PURE) study.

There are limited data on individual risk factors for SARS-CoV-2 infection (including unrecognized infection). In this seroepidemiologic substudy of an ongoing prospective cohort study of community-dwelling adults, participants were thoroughly characterized pre-pandemic. The SARS-CoV-2 infection was ascertained by serology. Among 8,719 participants from 11 high-, middle-, and low-income countries, 3,009 (35%) were seropositive for SARS-CoV-2. Characteristics independently associated with seropositivity were younger age (odds ratio, OR; 95% confidence interval, CI, per five-year increase: 0.95; 0.91-0.98) and body mass index >25 kg/m2 (OR, 95% CI: 1.16, 1.01-1.34). Smoking (as compared with never smoking, OR, 95% CI: 0.83, 0.70-0.97) and COVID-19 vaccination (OR, 95% CI: 0.70, 0.60-0.82) were associated with a reduced risk of seropositivity. Among seropositive participants, 83% were unaware of having been infected with SARS-CoV-2. Seropositivity and a lack of awareness of infection were more common in lower-income countries. The COVID-19 vaccination reduces the risk of SARS-CoV-2 infection (including recognized and unrecognized infections). Overweight or obesity is an independent risk factor for SARS-CoV-2 infection. Infection and lack of infection awareness are more common in lower-income countries.IMPORTANCEIn this large, international study, evidence of SARS-CoV-2 infection was obtained by testing blood specimens from 8,719 community-dwelling adults from 11 countries. The key findings are that (i) the large majority (83%) of community-dwelling adults from several high-, middle-, and low-income countries with blood test evidence of SARS-CoV-2 infection were unaware of this infection-especially in lower-income countries; and (ii) overweight/obesity predisposes to SARS-CoV-2 infection, while COVID-19 vaccination is associated with a reduced risk of SARS-CoV-2 infection. These observations are not attributable to other individual characteristics, highlighting the importance of the COVID-19 vaccination to prevent not only severe infection but possibly any infection. Further research is needed to understand the mechanisms by which overweight/obesity might increase the risk of SARS-CoV-2 infection.

Association between impaired lung function and carotid intima-media thickness in children.

Association between obstructive lung function impairment with higher cIMT is present in childhood after accounting for common risk factors. This suggests that a developmental link between obstructive lung diseases and CVD may have its origin in early life. https://bit.ly/4657s2b.

Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19.

BACKGROUND: The immune response in COVID-19 is characterized by the release of alarmin cytokines, which play crucial roles in immune activation and inflammation. The interplay between these cytokines and genetic variations may influence disease severity and outcomes, while sex differences might further contribute to variations in the immune response. METHODS: We measured the levels of alarmin cytokines in a cohort of COVID-19 and non-COVID-19 patients using a sensitive Meso Scale Discovery system. Additionally, we conducted an SNP analysis to identify genetic variations within the IL-33 and TSLP genes. The association between these genetic variations, cytokine production, and COVID-19 severity was examined. RESULTS: Our findings revealed elevated levels of IL-33 and IL-25 in COVID-19-positive patients compared to COVID-19-negative patients (p < 0.05), indicating their potential as therapeutic targets for disease modulation. Moreover, a minor allele within the IL-33 gene (rs3939286) was found to be associated with a protective effect against severe COVID-19 (p < 0.05), and minor alleles of the TSLP gene (rs2289276 and rs13806933) were found to significantly reduce TSLP protein levels in serum (p < 0.05). Sex-specific effects of TSLP and IL-33 SNPs were observed, suggesting a potential influence of sex hormones and genetic variations on the regulation of cytokine production. CONCLUSION: The present study highlights the importance of alarmin cytokines and genetic variations in COVID-19 severity, providing valuable insights into personalized treatment approaches. Our results suggest that targeting alarmin cytokines may offer potential therapeutic benefits in managing COVID-19. Furthermore, the sex-specific effects of genetic variations emphasize the need to consider individual genetic profiles and sex differences when designing targeted interventions.

Prediction of Lung Function Status Using Handgrip Strength and Anthropometry among the Healthy Malay Population in Malaysia.

Lung function depends primarily on the strength of the intercostal muscles and the diaphragm, which is indirectly related to handgrip strength (HGS). This study aims to determine the predictability of lung functions using HGS among healthy adults of Malay ethnicity in Malaysia. This study also aims to compare the equation using HGS with equations without HGS, such as the Global Lung Initiative (GLI). This study was carried out among adults between 35 to 70 years of age residing in urban and rural Malaysia. A series of standardized questionnaires were used to collect socio-demographic information. Lung functions were measured using a portable spirometer and HGS was measured using a Jamar dynamometer. The predictability of lung function indices (FEV1 and FVC) using HGS, age, and height was determined using multiple linear regression (MLR). Prediction of lung function indices was also generated using models without HGS for comparison with the equation that used HGS from this study. Pearson correlation analysis showed that both dominant (r = 0.49; p < 0.001) and non-dominant (r = 0.58; p < 0.001) HGS had a moderate significant correlation with lung function. In the MLR model, HGS was a significant (p < 0.001) predictor of lung function indices (FEV1 and FVC). The correlation of the predicted and measured lung indices using the equation generated in this study, which includes HGS, was higher compared with other lung function test equations that do not include HGS. The equations from MLR could be used to predict lung function indices among healthy Malay adults. The measurement of HGS may be used as a screening tool for lung function status when spirometry is unavailable.

Comparison of three dosing intervals for the primary vaccination of the SARS-CoV-2 mRNA Vaccine (BNT162b2) on magnitude, neutralization capacity and durability of the humoral immune response in health care workers: A prospective cohort study.

OBJECTIVES: The dosing interval of a primary vaccination series can significantly impact on vaccine immunogenicity and efficacy. The current study compared 3 dosing intervals for the primary vaccination series of the BNT162b2 mRNA COVID-19 vaccine, on humoral immune response and durability against SARS-CoV-2 ancestral and Beta variants up to 9 months post immunization. METHODS: Three groups of age- and sex-matched healthcare workers (HCW) who received 2 primary doses of BNT162b2 separated by 35-days, 35-42 days or >42-days were enrolled. Vaccine induced antibody titers at 3 weeks, 3 and 6-9 months post-second dose were assessed. RESULTS: There were 309 age- and sex-matched HCW (mean age 43 [sd 13], 58% females) enrolled. Anti-SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibody titers showed significant waning in levels beyond 35 days post first dose. The second dose induced a significant rise in antibody titers, which peaked at 3 weeks and then declined at variable rates across groups. The magnitude, consistency and durability of response was greater for anti-Spike than anti-RBD antibodies; and for IgG than IgA or IgM. Compared to the shorter schedules, a longer interval of >42 days offered the highest binding and neutralizing antibody titers against SARS-CoV-2 ancestral and Beta (B1.351) variants beyond 3 months post-vaccination. CONCLUSIONS: This is the first comprehensive study to compare 3 dosing intervals for the primary vaccination of BNT162b2 mRNA COVID-19 vaccine implemented in the real world. These findings suggest that delaying the second dose beyond 42 days can potentiate and prolong the humoral response against ancestral and Beta variants of SARS-CoV-2 up to 9 months post-vaccination.

Household Air Pollution and Adult Lung Function Change, Respiratory Disease, and Mortality across Eleven Low- and Middle-Income Countries from the PURE Study.

BACKGROUND: Globally, household air pollution (HAP) is a major environmental hazard that affects respiratory health. However, few studies have examined associations between HAP and lung function decline and respiratory disease and mortality. METHODS: We used data from the Prospective Urban and Rural Epidemiology study and examined adults residing in 240 rural communities in 11 low- and middle-income countries where HAP from cooking with solid fuels is common. Spirometry was conducted for 28,574 individuals at baseline and 12,489 individuals during follow-up (mean of 8 y between spirometry measures). In cross-sectional analyses, we compared lung function measurements [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio] in those who used solid fuels for cooking in comparison with clean fuels. Using repeated measurements of lung function, we examined the percent change in lung function measures per year, comparing individuals by baseline fuel type and individuals who used solid fuels at baseline but switched to clean fuels during follow-up. We also examined associations with prospective health events (any respiratory diseases, respiratory disease hospitalizations, and all-cause mortality). RESULTS: In adjusted cross-sectional models, use of solid fuel in comparison with clean fuels was associated with lower FEV1 of -17.5mL (95% CI: -32.7, -2.3) and FVC of -14.4mL (95% CI: -32.0, 3.2), but not FEV1/FVC. In longitudinal analyses, individuals who switched from solid fuels to clean cooking fuels during follow-up (n=3,901, 46% of those using solid fuel at baseline), showed no differences in the annual rate of change in FEV1 or FVC, but had small improvements in FEV1/FVC change (0.2% per year, 95% CI: 0.03, 0.3). Individuals who switched from solid to clean fuels had a decreased hazard ratio for respiratory events of 0.76 (95% CI: 0.57, 1.00) in comparison with persistent solid fuel users, which was not attenuated by lung function measures. CONCLUSION: We observed modest associations between HAP exposure and lung function, lung function change, and respiratory disease and mortality. https://doi.org/10.1289/EHP11179.

Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma.

RATIONALE: Extensive evidence in animal models supports a role for IL-13 in the pathobiology of asthma. IMA-638 and IMA-026 are fully humanized IgG(1) antibodies that bind to different epitopes and neutralize IL-13 bioactivity. OBJECTIVES: We hypothesized that anti-IL-13 treatment would inhibit allergen-induced late-phase asthmatic responses, airway hyperresponsiveness, and inflammation in subjects with asthma. METHODS: Fifty-six subjects with mild, atopic asthma were recruited for two double-blind, randomized, placebo-controlled, parallel group trials to compare IMA-638 and IMA-026 IL-13 antibody treatments with placebo treatment. Drug was administered on Days 1 and 8, and allergen challenges were performed on Days 14 and 35. The primary outcome variable was the late-phase area under the curve (AUC), and secondary outcome variables were the early- and late-phase maximum percent fall in FEV(1), early AUC, allergen-induced shift in airway hyperresponsiveness, and sputum eosinophils. MEASUREMENTS AND MAIN RESULTS: The treatment difference with IMA-638 on Day 14 was -19.1 FEV(1) × hour (95% confidence interval: -36.2, -1.9) for the allergen-induced early AUC and -23.8 FEV(1) × hour (95% confidence interval: -46.4, -1.2) for the late AUC (both P < 0.05), but this effect was lost by Day 35. Treatment with IMA-026 did not attenuate the asthmatic responses on Day 14 or Day 35. There was no effect of either antibody on allergen-induced airway hyperresponsiveness or sputum eosinophils. The frequency of adverse events after administration of the IL-13 antibodies was similar to placebo. CONCLUSIONS: IL-13 has a role in allergen-induced airway responses in humans. Further study is required to determine whether anti-IL-13 monoclonal antibodies will be beneficial clinically.