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This article describes a direct comparison between two symmetrical airfoils undergoing dynamic stall at high, unsteady reduced frequencies under otherwise identical conditions. Particle image velocimetry (PIV) was performed to distinguish the differences in flow structure between a NACA 0021 and a NACA 0012 airfoil undergoing dynamic stall. In addition, surface pressure measurements were performed to evaluate aerodynamic load and investigate the effect of laminar separation bubbles and vortex structures on the pressure fields surrounding the airfoils. Airfoil geometry is shown to have a significant effect on flow structure development and boundary layer separation, with separation occurring earlier for thinner airfoil sections undergoing constant pitch-rate motion. Inertial forces were identified to have a considerable impact on the overall force generation with increasing rotation rate. Force oscillation was observed to correlate with multiple vortex structures shedding at the trailing-edge during high rotation rates. The presence of laminar separation bubbles on the upper and lower surfaces was shown to dramatically influence the steady-state lift of both airfoils. Poststall characteristics are shown to be independent of airfoil geometry such that periodic vortex shedding was observed for all cases. However, the onset of deep stall is delayed with increased nondimensional pitch rate due to the delay in initial dynamic-stall vortex. [ABSTRACT FROM AUTHOR]

Post-stall flow structure and surface pressures are evaluated to determine the effects of large angles of attack, perching like manoeuvres on the flow about a NACA 0021 airfoil exposed to dynamic stall. Phase-averaged particle image velocimetry was performed to assess the load development during the constant angular velocity pitch-up motion and in post-stall conditions. Evaluation of the resultant aerodynamic loads indicates that initial airfoil rotation generates significant delays in force response. Furthermore, the reduced frequency is shown to influence the angle of attack at which deep stall is initiated, to the extent that fully separated flows are delayed to an angle of attack of 60°. Vortex structures are linked to lower surface pressures with increased angle of attack and also for post-stall flow conditions. Likewise, the presence of the vortex structures shifts the centre of pressure significantly along the airfoil chordline immediately after cessation of the airfoil rotation. At the maximum angle of attack, the centre of pressure is shown to move aft for fully separated flow conditions. The variation in location of the centre of pressure, not only changes the moment generation and aero-elastic characteristics of the airfoil, but also increases structural torsional loading and fluctuations that result in increased fatigue of helicopter rotor shafts and horizontal-axis wind turbines. [ABSTRACT FROM AUTHOR]

The present study was designed to study the chemical composition, apparent and true metabolizable energy values of the walnut meal and to evaluate the effects of different levels of walnut meal (0, 10, 20 and 30%) on Japanese quail's growth performance, blood metabolites, relative weight of different organs, malondialdehyde (MDA) concentration in breast meat and egg yolks' cholesterol. This study was conducted as a completely randomize design with 288 unsexed Japanese quails randomly dividing into 4 treatments with 4 replicates of 18 birds each. As a result of this study, no significant differences were found for feed intake and feed conversion ratio (P>0.05), except the birds fed 30% walnut meal showed lower weight gain compared to the control at 7-21 days of age (P<0.05). There were no significant differences in serum glucose, uric acid, serum aspartate aminotranspherase (AST) and alanine aminotranspherase (ALT) activities between different dietary treatments. The serum low density lipoprotein (LDL), cholesterol and triglyceride tended to decrease linearly (P<0.01) as the walnut meal levels were increased. The serum high density lipoprotein (HDL) level in quails fed 10% walnut meal were significantly higher than control group (P<0.05). Consumption of different levels of walnut meal significantly decreased malondialdehyde (MDA) concentration in breast meat of chicks aged 42 d (P<0.01). Different dietary treatments had no effect on the relative weight of different organs and carcass traits. In general, walnut meal is a good source of energy (apparent metabolizable energy corrected for nitrogen (AMEn) 3689 kcal/kg), oil (23%) and crude protein (40%) and could be used up to 20% for young chicks and 30% for older chicks, without any adverse effect on growth performance. [ABSTRACT FROM AUTHOR]

Self-sustained oscillations of the grazing flow along the orifice of a Helmholtz resonator were considered numerically. These fluctuations are driven by hydrodynamic instabilities inside the shear layer and the resonant acoustical field. Quantitative prediction of this process requires accurate calculations of grazing flow characteristics over the three dimensional resonator. In this paper flow excitation phenomenon assumed to be associated with external pressure fluctuations within the turbulent boundary layer of grazing flow and acoustic response of the cavity. To this end a Large Eddy Simulation (LES) of the three dimensional shear flow over the orifice carried out at a low Mach number to allow predictions of the amplitude and frequency of the pressure and velocity fluctuations. For validation propose, for pressure fluctuations inside the cavity, a good quantitative agreement with published data was obtained. Therefore the simulations provide an ability to predict the resonating frequency, pressure and velocity field for different inlet conditions. [ABSTRACT FROM AUTHOR]

The jetting characteristics of dielectric barrier discharge (DBD) actuators make these devices suitable for augmenting boundary layer flows. The associated change to the hydrodynamic stability of the fluid arising from the actuator provides a mechanism through which a DBD-based laminar flow control (LFC) system can be developed. Historically, DBD actuators with electrodes arranged parallel to each other have been used for LFC with mixed results. An alternative is to use an actuator with electrodes placed orthogonally to each other. Orthogonally arranged actuators exhibit different jetting characteristics to conventional ones, and as such understanding the effect that these actuators have on the mean velocity profile within a flat plate boundary layer is of significant interest to the development of DBD-based LFC technology. In this investigation, the velocity distribution within a flat plate boundary layer in a zero pressure gradient is measured in response to the operation of an orthogonally arranged actuator. The results suggest that significant thinning of the boundary layer can be realized with an orthogonally arranged actuator, over a short distance downstream of the device, and used in conjunction with a subtle suction effect, this thinning can be exacerbated. However, further downstream, rapid thickening of the layer, supported by a decrease in the shape factor of the flow suggests that the layer becomes unstable, in an accelerated fashion, to the presence of the actuator. Hence the stability of the layer is found to be significantly altered by the presence of the orthogonally arranged actuator, a requisite for a LFC system. However, since the actuator produces a destabilizing effect, the development of a successful LFC system based on orthogonal actuators will require further work. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To investigate the potential effects of lifetime cumulative ozone (O3) exposure on acute pulmonary responses to O3. METHODS:: Fifteen healthy subjects from a larger cohort of young adults were exposed to 200 ppb O3 for 4 hours followed by bronchoscopy and bronchoalveolar lavage 18 hours later. Lung function, symptom questionnaires, and blood samples were obtained before and after each exposure. Subjects' lifetime cumulative O3 exposures were estimated from residential histories and air-quality monitoring data. RESULTS:: Acute exposure to O3 caused decrements in forced expiratory volume in 1 second (FEV1), maximal mid-expiratory flow rate (FEF25-75), and forced expiratory flow rate at 75% of forced vital capacity (FEF75), and an increase in plasma clara cell protein (CC16) level. Changes in CC16 and lower respiratory symptoms, but not in lung function, were positively correlated with lifetime cumulative O3 exposure. CONCLUSION:: Higher lifetime cumulative O3 exposure was associated with airway injury and respiratory symptom responses, but not with airway inflammatory or lung function responses, to acute O3 exposure. [ABSTRACT FROM AUTHOR]

Rationale: Repeated, short-term exposures to ozone (O3) lead to attenuation of the acute lung function and airway inflammatory responses seen after a single exposure in healthy subjects, but it is unclear whether these acute responses also attenuate in subjects with asthma.Objective: To address this question by exposing 14 subjects with asthma to 0.2 ppm O3 for either 4 hours on a single day or 4 hours on 4 consecutive days (multiday [MD]). At least 3 weeks later, subjects underwent the alternate exposure.Methods: Spirometry was performed immediately pre- and postexposure and bronchoalveolar lavage (BAL) was obtained 18 hours after each exposure.Main Results: The decrease in FEV1 was greatest across Day 2 of the MD (MD2) exposure and then gradually declined on successive days of the MD exposure (mean +/- SD decrease in FEV1 of 25.4 +/- 18.0% across MD2 compared with 4.2 +/- 6.5% across MD4). Respiratory symptoms followed a similar pattern to that of FEV1. Although the concentration of neutrophils in BAL after the MD4 exposure was not significantly different from that after the single-day exposure (1.7 +/- 1.3 x 10(4) cells/ml vs. 1.2 +/- 0.8 x 10(4) cells/ml, p = 0.20), the concentration of alveolar macrophages did significantly increase in BAL after the MD exposure (19.9 +/- 9.7 x 10(4) cells/ml after MD4 vs. 12.1 +/- 6.4 x 10(4) cells/ml after the single day).Conclusions: Alveolar macrophages are recruited to the airways of subjects with asthma with repeated short-term exposures to O3, suggesting a possible role for these cells in the chronic response to oxidant-induced injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 μg) plus glycopyrrolate (15.6 μg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George’s Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS: A total of 535 participants underwent randomization. In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, −2.6 percentage points; 95% confidence interval [CI], −11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P=0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and −0.09 percentage points (95% CI, −1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, −0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS: Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry. (Funded by the National Heart, Lung, and Blood Institute and others; RETHINC ClinicalTrials.gov number, NCT02867761. opens in new tab.) [ABSTRACT FROM AUTHOR]

The cardiovascular effects of ozone exposure are unclear. Using measurements from the 87 participants in the Multicenter Ozone Study of oldEr Subjects (MOSES), we examined whether personal and ambient pollutant exposures before the controlled exposure sessions would be associated with adverse changes in pulmonary and cardiovascular function. We used mixed effects linear regression to evaluate associations between increased personal exposures and ambient pollutant concentrations in the 96 h before the pre-exposure visit, and 1) biomarkers measured at pre-exposure, and 2) changes in biomarkers from pre-to post-exposure. Decreases in pre-exposure forced expiratory volume in 1 s (FEV 1) were associated with interquartile-range increases in concentrations of particulate matter ≤2.5 μm (PM 2.5) 1 h before the pre-exposure visit (−0.022 L; 95% CI -0.037 to −0.006; p = 0.007), carbon monoxide (CO) in the prior 3 h (−0.046 L; 95% CI -0.076 to −0.016; p = 0.003), and nitrogen dioxide (NO 2) in the prior 72 h (−0.030 L; 95% CI -0.052 to −0.008; p = 0.007). From pre-to post-exposure, increases in FEV 1 were marginally significantly associated with increases in personal ozone exposure (0.010 L; 95% CI 0.004 to 0.026; p = 0.010), and ambient PM 2.5 and CO at all lag times. Ambient ozone concentrations in the prior 96 h were associated with both decreased pre-exposure high frequency (HF) heart rate variability (HRV) and increases in HF HRV from pre-to post-exposure. We observed associations between increased ambient PM 2.5 , NO 2 , and CO levels and reduced pulmonary function, and increased ambient ozone concentrations and reduced HRV. Pulmonary function and HRV increased across the exposure sessions in association with these same pollutant increases, suggesting a "recovery" during the exposure sessions. These findings support an association between short term increases in ambient PM 2.5 , NO 2 , and CO and decreased pulmonary function, and increased ambient ozone and decreased HRV. • We assessed effects of ambient pollutants in a large controlled exposure study. • Increased ambient PM 2.5 , NO 2 , and CO were associated with reduced lung function. • Increased ambient ozone (but not controlled ozone) reduced heart rate variability. • These effects reversed with breathing cleaner indoor air during study sessions. [ABSTRACT FROM AUTHOR]

Multi-mode Wave Energy Converters (WECs) are able to harvest energy from multiple Degrees-of-Freedom (DOFs) simultaneously, which increases the power that can be absorbed from the incident wave compared to single-DOF WECs. However, nonlinear coupling between hydrodynamic modes, which occurs when the WEC oscillates simultaneously in multiple directions, means that simply applying the typical control strategies used for single-DOF WECs can lead to sub-optimal performance. This study investigates the multi-DOF dynamic control of a submerged, flat cylindrical WEC subjected to hydrodynamic coupling effects modelled under the weakly nonlinear potential flow theory based on the weak-scatterer approximation. Results show that, at low incident wave frequencies, tuning the surge, heave and pitch modes of the WEC to the same natural frequency can result in power losses of up to 30% in the weakly nonlinear model compared to results obtained from a fully linear model. These discrepancies are attributed to the pitching motions of the WEC, which changes the projected surface area of the device relative to the equilibrium position and hence violates the assumptions of the linear theory. From these findings, a suggested design strategy where the surge, heave and pitch DOFs were all decoupled and tuned to different natural frequencies was therefore proposed. In the presence of weakly nonlinear hydrodynamic coupling, it was found that this design may result in significant improvements in power absorbed for the multi-mode WEC, compared to a case where all DOFs are simply tuned to match the peak frequency of a given sea state. • Nonlinear coupling between hydrodynamic modes greatly impacts multi-mode WEC power. • Tuning the pitch, surge and heave modes to the same natural frequency reduces power. • Tuning each mode to a different frequency may increase broadband power absorbed. • Pitch changes the projected surface area, and hence power absorbed by other modes. • Pitch should be tuned to a higher frequency to improve performance. [ABSTRACT FROM AUTHOR]

• Pitch reduces maximum power when nonlinear pitch-surge coupling is included. • Pitch phase must be tuned to absorb maximum power in the nonlinear system. • Power absorbed becomes more sensitive to phase as pitch-surge coupling increases. • Combined pitch-surge motions result in superharmonics in the hydrodynamic forces. • Hydrodynamic force amplitudes and phases change with pitch, affecting control. Multi-mode wave energy converters are able to generate power from multiple degrees-of-freedom, typically delivering increased power absorption from ocean waves compared to devices operating in heave or surge only. However, the control of such systems is complex due to strong coupling between different degrees-of-freedom. This study aims to understand the effect of both linear and nonlinear pitch-surge hydrodynamic coupling on the performance of a submerged cylindrical wave energy converter. Results showed that when nonlinear coupling effects were considered, pitch had a much larger effect on device performance than what was predicted from a linear model. The maximum power that could be absorbed by the device at lower frequencies was significantly reduced as pitch amplitude increased. In terms of control, from linear theory, for any given pitch amplitude and phase, only the surge amplitude and phase was required to tune the device for maximum power absorption from the wave. However, when a nonlinear model was used, results showed that proper tuning of the pitch phase was also required to achieve maximum power absorption. As the pitch amplitude increased, nonlinear hydrodynamic effects caused by the combined pitch-surge motions became more significant, which in turn affected power estimates. Care should therefore be taken, since linear hydrodynamic models could potentially provide misleading predictions regarding the performance and control of multi-mode wave energy converters. [ABSTRACT FROM AUTHOR]

In this paper, we quantified the heat transfer coefficient (HTC) of Fe 3 O 4 aqueous nano-suspension at various mass concentrations of 0.05% 0.2%. The potential role of operating parameters including heat flux perpendicular to the surface (HF), concentration of the nanoparticle (NP), strength of magnetic field (MF), zeta potential and concentration of a specific surfactant on HTC, critical heat flux (CHF) and transient fouling resistance of the surface was identified. Results showed that MF can lower the fouling resistance providing that the nano-suspension is stable. It was shown that in this case, the HTC value was also promoted. However, the enhancement of HTC strongly depended on the zeta potential value. Likewise, by increasing the NP concentration, the CHF value was augmented, while the HTC was promoted u to wt. % = 0.15 and then decreased at wt. % = 0.2. This behavior was attributed to the existence of a thermal resistance on the surface. Notably, the bubble formation on the surface was intensified due to the MF, which was attributed to the formation of irregularities and micro-cavities due to the deposition of the NPs. • The pool boiling heat transfer to Fe3O4/water nanofluid was conducted. • Critical heat flux and heat transfer coefficient were quantified in pool boiling. • Influence of magnetic field on boiling thermal performance was analyzed. • Bubble formation under the magnetic field was visualized. [ABSTRACT FROM AUTHOR]

• Performance of a new catalyst mediated in a micro-reactor was assessed. • The catalyst preparation method is convenient and cost-effective. • Response surface methodology was used to optimise the operating conditions. • The methanol conversion extent reached 100% at 773 K. • Length and aspect ratio had no influence on the methanol conversion extent. In the present work, the chemical performance of a new catalyst mediated inside a micro-reactor for hydrogen production was experimentally assessed. The coated catalyst was prepared via particulate fouling technique by uniformly dispersing copper nano-flakes on silica as a conductive substrate. The catalyst was calcinated at 973 K to further strengthen the structure against creep and flow friction forces. The proposed method is a cost-effective technique for the production of catalyst, which in turn improves the economic viability of the hydrogen production with micro-reactors. The effect of different operating parameters such as temperature, velocity of the reactants, the amount of the catalyst coated on the walls of the reactor and the geometrical specifications of the micro-reactor on methanol conversion extent was experimentally studied. The stability of the catalyst was also examined and it was demonstrated that the mechanism of hydrogen and synthetic gas production with the proposed catalyst is diffusion-controlled such that with an increase in the flow rate of the reactants, the residence time decreased resulting in the reduction of methanol conversion extent. For an average velocity of 24000 ml/(g hr) at T = 773 K, the methanol conversion exceeded 97%. Likewise, using response surface methodology, the operation of the micro-reactor was optimised such that the methanol conversion was promoted to 100% at 773 K at catalyst loading of 1.0 g and velocity of 24000 ml/(g hr). [ABSTRACT FROM AUTHOR]

Background- Among tobacco-exposed persons with preserved spirometry (TEPS), we previously demonstrated that different lung volume indices, specifically elevated total lung capacity (TLC) versus elevated ratio of functional residual capacity-to-TLC (FRC/TLC), identify different lung disease characteristics in the COPDGene cohort. Objective- Determine differential disease characteristics and trajectories associated with the lung volume indices among TEPS in the SPIROMICS cohort. Methods- We categorized TEPS (n=814) by tertiles (low, intermediate, high) of TLC or residual volume-to-TLC (RV/TLC) derived from baseline CT images, and then examined clinical and spirometric disease trajectories in mutually exclusive categories of participants with high TLC without high RV/TLC ([TLC] high ) versus high RV/TLC without high TLC ([RV/TLC] high ). We examined differences in CT-measured emphysema (HU≤-950; PRM EMPH ), airway trapping (HU≤-856; PRM fSAD ; DPM GasTrap ), and airway geometry (Pi10), respiratory symptoms (mMRC; CAT; SGRQ; SF12), and outcomes (annualized exacerbation rate) between the two categories at baseline and over follow-up time up to 8.5 years, using regression modeling adjusted for age, sex, height, weight, and smoking status (current versus former) and burden (pack-years). Results- In TEPS participants, the pattern of spirometric disease progression differed between [TLC]high and [RV/TLC] high : increased FVC with stable FEV 1 in [TLC] high versus unchanged FVC but nominally decreased FEV 1 in [RV/TLC] high . Compared to [TLC] high , TEPS with [RV/TLC] high had less emphysema (by HU≤-950) but more airway disease (by HU≤-856; PRM fSAD ; DPM GasTrap , and Pi10), more respiratory symptoms (by mMRC; CAT; SGRQ; SF12), and more severe exacerbations at baseline. Over an average follow-up time of 4.1±2.4 years (range: 0.5 to 8.5 years), [RV/TLC] high TEPS also had higher likelihood of developing more severe spirometric disease (PRISm or GOLD-2) and worsening of their respiratory symptoms (by CAT and SGRQ). Although the incidence rates of respiratory exacerbations, hospitalizations, and mortality were not different between the two categories over the follow-up time, [RV/TLC] high TEPS were more likely to have been placed on a respiratory inhaler at their last follow-up visit. Conclusions- In these TEPS from SPIROMICS cohort, lung volume stratification by TLC versus RV/TLC identifies two pre-COPD phenotypes with distinct respiratory symptoms, radiographic features, and clinical trajectories. The characteristics of these pre-COPD phenotypes match those previously described from COPDGene cohort using TLC versus FRC/TLC stratification.

Rationale: Individuals with chronic obstructive pulmonary disease (COPD) have airflow obstruction and maldistribution of ventilation. For those living at high altitude, any gas exchange abnormality is compounded by reduced partial pressures of inspired oxygen. Objectives: Does residence at higher altitude exposure affect COPD outcomes, including lung function, imaging characteristics, symptoms, health status, functional exercise capacity, exacerbations, and mortality? Methods: From the SPIROMICS (Subpopulation and Intermediate Outcome Measures in COPD Study) cohort, we identified individuals with COPD living below 1,000 ft (305 m) elevation ( n  = 1,367) versus above 4,000 ft (1,219 m) elevation ( n  = 288). Multivariable regression models were used to evaluate associations of exposure to high altitude with COPD-related outcomes. Measurements and Main Results: Living at higher altitude was associated with reduced functional exercise capacity as defined by 6-minute-walk distance (-32.3 m [95% confidence interval, -49.8 to -14.8 m]). There were no differences in patient-reported outcomes as defined by symptoms (COPD Assessment Test and modified Medical Research Council dyspnea scale), or health status (St. George's Respiratory Questionnaire). Higher altitude was not associated with a different rate of FEV 1 decline. Higher altitude was associated with lower odds of severe exacerbations (incidence rate ratio, 0.65 [95% confidence interval, 0.46 to 0.90]). There were no differences in small airway disease, air trapping, or emphysema. In longitudinal analyses, higher altitude was associated with increased mortality (hazard ratio, 1.25 [95% confidence interval, 1.0 to 1.55]); however, this association was no longer significant when accounting for air pollution. Conclusions: Long-term altitude exposure is associated with reduced functional exercise capacity in individuals with COPD, but this did not translate into differences in symptoms or health status. In addition, long-term high-altitude exposure did not affect progression of disease as defined by longitudinal changes in spirometry. Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

Background: Sarcoidosis is an idiopathic multiorgan disease with variable clinical outcomes. Comprehensive analysis of sarcoidosis mortality in US veterans is lacking., Research Question: What are the trends in all-cause mortality among US veterans with sarcoidosis, and how are these trends influenced by demographics, Black vs White racial disparities, and geographic variability in relationship to mortality?, Study Design and Methods: Using Veterans Health Administration (VHA) electronic health records (EHRs), we conducted a population-based retrospective cohort study of adjusted all-cause mortality from 2004 through 2022 among veterans with a diagnosis of sarcoidosis who received care through the VHA. Demographics, region of residence, service branch, tobacco use, and comorbidities were extracted from the EHR. Annual trends in all-cause mortality and patient-level characteristics associated with mortality were examined with multivariable ungrouped Poisson regression. We visualized trends and analyzed state-by-state mortality using the marginal means procedure. In subgroup analysis (2015-2022), we considered the impact of neighborhood-level socioeconomic disparities using the area deprivation index (ADI)., Results: In all, 23,745 veterans received a diagnosis of sarcoidosis between 2004 and 2019 and were followed up through 2022. After adjustment, including age and sex, all-cause mortality increased annually by 4.7% (P < .0001) and was 6.4% higher in Black than White veterans (mortality rate ratio, 1.064; P = .02). A subgroup analysis comparing models with and without ADI adjustment showed no meaningful change in mortality trends. Risk factors for increased all-cause mortality included older age, male sex, Black race, Northeast residence, and lower risk with other service branches. Despite distinct geographical variations in mortality rates, no clear patterns emerged., Interpretation: Mortality among veterans with sarcoidosis is rising. Differences identified by service branch and higher risk among male Veterans raise questions about differences in environmental exposures. The narrower racial disparities and smaller impact of ADI than in other studies may highlight the role of universal health care access in achieving equitable outcomes., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: M. A. reports grants from the Departments of Defense [Grant W81XWH-20-1-0158] and Veterans Affairs [Grant CXV-00125], and financial support from Guardant Health and Genentech during the conduct of the study. M. A. W. reports financial support from the US Veterans Health Administration, the National Institute of Health—NCATS, and McGraw Hill Education. None declared (M. I. S., M. T. A., A. D. B., W. F. G., S. M. N., K. F. G., C. E. M., L. L. K.)., (Published by Elsevier Inc.)

The relationship between measures of stenosis and microvascular resistance is of importance due to medical decisions being based on these values. This research investigates the impact of varying microvascular resistance on fractional flow reserve (FFR) and hyperaemic stenosis resistance (hSR). Microvascular resistance is classified using hyperaemic microvascular resistance (hMR). Additionally, hMR using the upstream pressure value (hMR Pa ) has also been calculated and is compared to hMR measured conventionally. Tests were conducted at three different degrees of stenosis (quantified by percent area) in a coronary flow circuit with varying downstream resistance to simulate the microvasculature. Pressure and flow values are recorded across the stenosed section, allowing for calculation of the diagnostic indexes. Results indicate that for a constant degree of stenosis, FFR would increase with increasing microvascular resistance while hSR would remain almost constant. hMR Pa was found to approach hMR as the stenosis severity decreased, and the pressure gradient decreased. In the results shown here, with sufficiently high downstream resistance, an 84 % stenosis could produce an FFR value over 0.8. This result suggests that there is the potential for misdiagnosis of the severity of stenosis when combined with elevated microvascular resistance. Consequently, decisions on the clinical significance of a stenosis, classified by FFR, need to consider the effect of the microvascular resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale: Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency., Objective: Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation., Methods: We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years)., Results: Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohen's Kappa = 0.47 ± 0.07; P < 0.001). Nevertheless, self-reported and EHR-identified m/s-AECOPD events were both associated with higher BAL neutrophils (ß ± SEM: 3.0 ± 1.1 and 1.3 ± 0.5 per 10% neutrophil increase; P ≤ 0.018) and lymphocytes (0.9 ± 0.4 and 0.7 ± 0.3 per 10% lymphocyte increase; P ≤ 0.041). Exacerbation by either measure combined was associated with a larger estimated effect (3.7 ± 1.2 and 1.0 ± 0.5 per 10% increase in neutrophils and lymphocytes, respectively) but was not statistically significantly different compared to the self-report only approach. Among the 184 TEPS participants, there were fewer moderate to very severe respiratory exacerbations by self-report (n = 15 or 8%) or EHR-documentation (n = 9 or 5%), but a similar level of agreement as those with COPD was observed (Cohen's Kappa = 0.38 ± 0.07; P < 0.001)., Discussion: While there is modest agreement between self-reported and EHR-identified m/s-AECOPD, events are missed by relying on either method alone. However, m/s-AECOPD quantified by self-report or health records is associated with BAL neutrophilia and lymphocytosis., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor (ACE2-OE) that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. Interferon-lambda was upregulated in cells with low-level infection while the NF-kB inhibitor alpha gene (encoding IkBa) was consistently upregulated in infected cells, and its expression positively correlated with infection levels. Confocal microscopy showed more IkBa expression in infected than bystander cells, but found concurrent nuclear translocation of NF-kB that IkBa usually prevents. Overexpressing a nondegradable IkBa mutant reduced NF-kB translocation and increased viral infection. These data demonstrate the functionality of ACE2-OE organoids in SARS-CoV-2 research and underscore that the strength of the NF-kB feedback loop in infected cells controls viral replication., (© 2024. The Author(s).)

Background: In tobacco-exposed persons with preserved spirometry (active smoking or secondhand smoke [SHS] exposure), air trapping can identify a subset with worse symptoms and exercise capacity. The physiologic nature of air trapping in the absence of spirometric airflow obstruction remains unclear. The aim of this study was to examine the underlying pathophysiology of air trapping in the context of preserved spirometry and to determine the utility of bronchodilators in SHS tobacco-exposed persons with preserved spirometry and air trapping., Methods: We performed a double-blinded placebo-controlled crossover randomized clinical trial in nonsmoking individuals at risk for COPD due to exposure to occupational SHS who had preserved spirometry and air trapping defined as either a residual volume-to-total lung capacity ratio (RV/TLC) > 0.35 or presence of expiratory flow limitation (EFL, overlap of tidal breathing on maximum expiratory flow-volume loop) on spirometry at rest or during cardiopulmonary exercise testing (CPET). Those with asthma or obesity were excluded. Participants underwent CPET at baseline and after 4-week trials of twice daily inhalation of 180 mcg of albuterol or placebo separated by a 2-week washout period. The primary outcome was peak oxygen consumption (VO 2 ) on CPET. Data was analyzed by both intention-to-treat and per-protocol based on adherence to treatment prescribed., Results: Overall, 42 participants completed the entire study (66 ± 8 years old, 91% female; forced expiratory volume in 1 s [FEV 1 ] = 103 ± 16% predicted; FEV 1 to forced vital capacity [FVC] ratio = 0.75 ± 0.05; RV/TLC = 0.39 ± 0.07; 85.7% with EFL). Adherence was high with 87% and 93% of prescribed doses taken in the treatment and placebo arms of the study, respectively (P = 0.349 for comparison between the two arms). There was no significant improvement in the primary or secondary outcomes by intention-to-treat or per-protocol analysis. In per-protocol subgroup analysis of those with RV/TLC > 0.35 and ≥ 90% adherence (n = 27), albuterol caused an improvement in peak VO 2 (parameter estimate [95% confidence interval] = 0.108 [0.014, 0.202]; P = 0.037), tidal volume, minute ventilation, dynamic hyperinflation, and oxygen-pulse (all P < 0.05), but no change in symptoms or physical activity., Conclusions: Albuterol may improve exercise capacity in the subgroup of SHS tobacco-exposed persons with preserved spirometry and substantial air trapping. These findings suggest that air trapping in pre-COPD may be related to small airway disease that is not considered significant by spirometric indices of airflow obstruction., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Despite the wealth of scientific information on the health effects of air pollution, the adult public's lifestyle continues to be largely detrimental towards the environment., Objective: The purpose of the study was to determine whether a short interactive teaching session on air pollution could shift reported behavioral choices of adolescents towards environmentally friendlier options., Methods: We performed a pilot randomized control trial in which eighth-grade students were randomized to receive a one-hour script-based teaching on either the effects of air pollution on lung health (intervention group) or the role of vaccination in public health (active control group). The enrolled students completed a survey (15 multiple-choice questions; five targeting understanding (score range 5 to 20); ten targeting behavioral choices (score range 10 to 38) newly designed for this study to evaluate their understanding and predict their future behavior towards air pollution immediately before, immediately after, and one month after the teaching sessions., Results: Seventy-seven students (age = 13.5±0.6 years; 50.4% female; median annual family income = $25K-$50K with 70.1% <$50K; 39 assigned to intervention group) were enrolled in the study. The teaching sessions did not result in any significant change in the participants' understanding domain scores in either the intervention or the control groups. However, the intervention (air pollution) teaching session resulted in a statistically significant increase in behavior domain score from baseline to immediately post-teaching, which continued to be present at one-month follow-up (mean ± standard deviation of score change immediately after = 1.7±3.3; score change 1-month after = 2.5±3.2; P<0.001; minimally important difference = 1.0)., Discussion: This pilot study highlights the potential of a short one-time teaching session in promoting environmentally friendly behavior choices among adolescents., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Rationale: Lung volumes identify the "susceptible smokers" who progress to develop spirometric COPD. However, among susceptible smokers, development of spirometric COPD seems to be heterogeneous, suggesting the presence of different pathological mechanisms during early establishment of spirometric COPD. The objective of the present study was to determine the differential patterns of radiographic pathologies among susceptible smokers., Methods: We categorised smokers with preserved spirometry (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0) in the Genetic Epidemiology of COPD (COPDGene) cohort based on tertiles (low, intermediate and high) of lung volumes (either total lung capacity (TLC), functional residual capacity FRC or FRC/TLC) at baseline visit. We then examined the differential patterns of change in spirometry and the associated prevalence of computed tomography measured pathologies of emphysema and airway disease with those categories of lung volumes., Results: The pattern of spirometric change differed when participants were categorised by TLC versus FRC/TLC: those in the high TLC tertile showed stable forced expiratory volume in 1 s (FEV 1 ), but enlarging forced vital capacity (FVC), while those in the high FRC/TLC tertile showed decline in both FEV 1 and FVC. When participants from the high TLC and high FRC/TLC tertiles were partitioned into mutually exclusive groups, compared to those with high TLC, those with high FRC/TLC had lesser emphysema, but greater air trapping, more self-reported respiratory symptoms and exacerbation episodes and higher likelihood of progressing to more severe spirometric disease (GOLD stages 2-4 versus GOLD stage 1)., Conclusions: Lung volumes identify distinct physiological and radiographic phenotypes in early disease among susceptible smokers and predict the rate of spirometric disease progression and the severity of symptoms in early COPD., Competing Interests: Conflict of interest: S. Zeng reports a grant from National Library of Medicine. Conflict of interest: G. Luo reports a grant from National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL142503). Conflict of interest: M. Arjomandi reports grants from the Departments of Defense (W81XWH-20-1-0158) and Veterans Affairs (CXV-00125), the Flight Attendant Medical Research Institute (012500WG and CIA190001), and the California Tobacco-related Disease Research Program (T29IR0715) during the conduct of the study. He has received research support from Guardant Health and Genentech. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Importance: People who smoked cigarettes may experience respiratory symptoms without spirometric airflow obstruction. These individuals are typically excluded from chronic obstructive pulmonary disease (COPD) trials and lack evidence-based therapies., Objective: To define the natural history of persons with tobacco exposure and preserved spirometry (TEPS) and symptoms (symptomatic TEPS)., Design, Setting, and Participants: SPIROMICS II was an extension of SPIROMICS I, a multicenter study of persons aged 40 to 80 years who smoked cigarettes (>20 pack-years) with or without COPD and controls without tobacco exposure or airflow obstruction. Participants were enrolled in SPIROMICS I and II from November 10, 2010, through July 31, 2015, and followed up through July 31, 2021., Exposures: Participants in SPIROMICS I underwent spirometry, 6-minute walk distance testing, assessment of respiratory symptoms, and computed tomography of the chest at yearly visits for 3 to 4 years. Participants in SPIROMICS II had 1 additional in-person visit 5 to 7 years after enrollment in SPIROMICS I. Respiratory symptoms were assessed with the COPD Assessment Test (range, 0 to 40; higher scores indicate more severe symptoms). Participants with symptomatic TEPS had normal spirometry (postbronchodilator ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity >0.70) and COPD Assessment Test scores of 10 or greater. Participants with asymptomatic TEPS had normal spirometry and COPD Assessment Test scores of less than 10. Patient-reported respiratory symptoms and exacerbations were assessed every 4 months via phone calls., Main Outcomes and Measures: The primary outcome was assessment for accelerated decline in lung function (FEV1) in participants with symptomatic TEPS vs asymptomatic TEPS. Secondary outcomes included development of COPD defined by spirometry, respiratory symptoms, rates of respiratory exacerbations, and progression of computed tomographic-defined airway wall thickening or emphysema., Results: Of 1397 study participants, 226 had symptomatic TEPS (mean age, 60.1 [SD, 9.8] years; 134 were women [59%]) and 269 had asymptomatic TEPS (mean age, 63.1 [SD, 9.1] years; 134 were women [50%]). At a median follow-up of 5.76 years, the decline in FEV1 was -31.3 mL/y for participants with symptomatic TEPS vs -38.8 mL/y for those with asymptomatic TEPS (between-group difference, -7.5 mL/y [95% CI, -16.6 to 1.6 mL/y]). The cumulative incidence of COPD was 33.0% among participants with symptomatic TEPS vs 31.6% among those with asymptomatic TEPS (hazard ratio, 1.05 [95% CI, 0.76 to 1.46]). Participants with symptomatic TEPS had significantly more respiratory exacerbations than those with asymptomatic TEPS (0.23 vs 0.08 exacerbations per person-year, respectively; rate ratio, 2.38 [95% CI, 1.71 to 3.31], P < .001)., Conclusions and Relevance: Participants with symptomatic TEPS did not have accelerated rates of decline in FEV1 or increased incidence of COPD vs those with asymptomatic TEPS, but participants with symptomatic TEPS did experience significantly more respiratory exacerbations over a median follow-up of 5.8 years.