Ensuring equitable access to guideline-based asthma care across the lifespan: Tips and future directions to the successful implementation of the new NAEPP 2020 guidelines, a Work Group Report of the AAAAI Asthma, Cough, Diagnosis, and Treatment Committee.

The most recent recommendations from the 2020 National Asthma Education and Prevention Program Update and Global Initiative for Asthma 2021 guide evidence-based clinical decision making. However, given the present state of health disparities by age, income, and race, the equitable implementation and dissemination of these guidelines will be unlikely without further guidance. This work group report reviews the current state of the new asthma guideline implementation; presents updated evidence-based therapeutic options with attention to specific patient populations; and addresses barriers to the implementation of these guidelines in minoritized, historically marginalized, and underresourced communities. Allergists and immunologists can use practical ways to accomplish the goals of improved asthma care access and advanced asthma care across the life span, with specific considerations to historically marginalized populations. Modifiable barriers to guideline implementation include financial barriers, environmental factors, and allergy subspecialty access and care coordination. Various programs to improve access to guideline-based asthma care include community programs, school-based asthma programs, and digital health solutions, with an emphasis on reducing disparities by race.

Rhinitis Disease Burden and the Impact of Social Determinants of Health.

Social determinants of health (SDHs) have a substantial impact on patient care and outcomes globally, both in low- to middle-income countries and in high-income countries. In the clinic, lack of availability of diagnostic tools, inequities in access to care, and challenges obtaining and adhering to prescribed treatment plans may further compound these issues. This article addresses a case of rhinitis in the context of SDHs and inequities in care that may affect various communities and populations around the world. SDHs may include various aspects of one's financial means, education, access to medical care, environment and living situation, and community factors, each of which could play a role in the rhinitis disease manifestations, diagnosis, and management. Allergic and nonallergic rhinitis are considered from this perspective. Rhinitis epidemiology, disease burden, and risk factors are broadly addressed. Patient evaluation, diagnostic tests, and management options are also reviewed, and issues related to SDHs are noted. Finally, inequities in care, knowledge gaps, and unmet needs are highlighted. It is critical to consider SDHs and care inequities when evaluating and treating patients for rhinitis and other allergic conditions.

Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study.

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

Unveiling Asthma's Complex Tapestry: Insights from Diverse Perspectives.

Asthma, a chronic respiratory disorder affecting millions worldwide, exhibits considerable heterogeneity in its clinical presentation, severity, and response to therapy [...].

Hematological Parameters for Predicting Mortality in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

(1) Introduction: COPD is a common and serious condition affecting a significant proportion of the population globally. Patients often suffer from exacerbations which lead to the worsening of their health status and respiratory function, and can often lead to death. Quick and cheap investigations are required that are capable of predicting mortality in patients with acute exacerbations that can be applied in low resource settings. (2) Materials and methods: This was a retrospective study carried out using hospital records of patients admitted for AECOPD from 1 January 2017 to 30 November 2022. Chi-square test (for sex) and Student's t-test were used to look for significant associations. Receiver Operating Characteristics (ROC) curves were plotted and Area Under Curve (AUC) values were calculated for various hematological parameters. Youden's J was used to identify the ideal cut-off with optimal sensitivity and specificity. Multivariate Cox regression was used to identify independent hematological predictors of mortality. Kaplan-Meir survival plots for neutrophil lymphocyte ratio (NLR) with the optimal cut-off were plotted. (3) Results: Amongst the 500 patients, 42 died while 458 survived, giving a mortality rate of 8.4%. NLR had the strongest association with mortality. The cut-off for various parameters were: NLR 14.83 (AUC 0.73), total leukocyte count (TLC) 13,640 cells/mm3 (AUC 0.60), absolute neutrophil count (ANC) 12,556 cells/mm3 (AUC 0.62), derived NLR (dNLR) 9.989 (AUC 0.73), hemoglobin 11.8 mg/dL (AUC 0.59), packed cell volume (PCV) 36.6% (AUC 0.60), and platelet lymphocyte ratio (PLR) 451.32 (AUC 0.55). (4) Conclusions: In patients with acute exacerbation of COPD, NLR was strongly associated with mortality, followed by dNLR. Cox regression identified NLR as an independent predictor of mortality.

A Proteomics Investigation of Cigarette Smoke Exposed Wistar Rats Revealed Improved Anti-Inflammatory Effects of the Cysteamine Nanoemulsions Delivered via Inhalation.

Cigarette smoking is the major cause of chronic inflammatory diseases such as chronic obstructive pulmonary disease (COPD). It is paramount to develop pharmacological interventions and delivery strategies against the cigarette smoke (CS) associated oxidative stress in COPD. This study in Wistar rats examined cysteamine in nanoemulsions to counteract the CS distressed microenvironment. In vivo, 28 days of CS and 15 days of cysteamine nanoemulsions treatment starting on 29th day consisting of oral and inhalation routes were established in Wistar rats. In addition, we conducted inflammatory and epithelial-to-mesenchymal transition (EMT) studies in vitro in human bronchial epithelial cell lines (BEAS2B) using 5% CS extract. Inflammatory and anti-inflammatory markers, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1ß, IL-8, IL-10, and IL-13, have been quantified in bronchoalveolar lavage fluid (BALF) to evaluate the effects of the cysteamine nanoemulsions in normalizing the diseased condition. Histopathological analysis of the alveoli and the trachea showed the distorted, lung parenchyma and ciliated epithelial barrier, respectively. To obtain mechanistic insights into the CS COPD rat model, "shotgun" proteomics of the lung tissues have been carried out using high-resolution mass spectrometry wherein genes such as ABI1, PPP3CA, PSMA2, FBLN5, ACTG1, CSNK2A1, and ECM1 exhibited significant differences across all the groups. Pathway analysis showed autophagy, signaling by receptor tyrosine kinase, cytokine signaling in immune system, extracellular matrix organization, and hemostasis, as the major contributing pathways across all the studied groups. This work offers new preclinical findings on how cysteamine taken orally or inhaled can combat CS-induced oxidative stress.

Discovery of Hybrid Thiouracil-Coumarin Conjugates as Potential Novel Anti-SARS-CoV-2 Agents Targeting the Virus's Polymerase "RdRp" as a Confirmed Interacting Biomolecule.

The coronavirus (COVID-19) pandemic, along with its various strains, has emerged as a global health crisis that has severely affected humankind and posed a great challenge to the public health system of affected countries. The replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly depends on RNA-dependent RNA polymerase (RdRp), a key enzyme that is involved in RNA synthesis. In this regard, we designed, synthesized, and characterized hybrid thiouracil and coumarin conjugates (HTCAs) by ether linkage, which were found to have anti-SARS-CoV-2 properties. Our in vitro real-time quantitative reverse transcription PCR (RT-qPCR) results confirmed that compounds such as 5d, 5e, 5f, and 5i inhibited the replication of SARS-CoV-2 with EC50 values of 14.3 ± 0.14, 6.59 ± 0.28, 86.3 ± 1.45, and 124 ± 2.38 µM, respectively. Also, compound 5d displayed significant antiviral activity against human coronavirus 229E (HCoV-229E). In addition, some of the HTCAs reduced the replication of SARS-CoV-2 variants such as D614G and B.617.2. In parallel, HTCAs in uninfected Vero CCL-81 cells indicated that no cytotoxicity was noticed. Furthermore, we compared the in silico interaction of lead compounds 5d and 5e toward the cocrystal structure of Suramin and RdRp polymerase with Remdesvir triphosphate, which showed that compounds 5d, 5e, and Remdesvir triphosphate (RTP) share a common catalytical site of RdRp but not Suramin. Additionally, the in silico ADMET properties predicted for the lead HTCAs and RTP showed that the maximum therapeutic doses recommended for compounds 5d and 5e were comparable to those of RTP. Concurrently, the pharmacokinetics of 5d was characterized in male Wistar Albino rats by administering a single oral gavage at a dose of 10 mg/kg, which gave a Cmax value of 0.22 µg/mL and a terminal elimination half-life period of 73.30 h. In conclusion, we established a new chemical entity that acts as a SARS-CoV-2 viral inhibitor with minimal or no toxicity to host cells in the rodent model, encouraging us to proceed with preclinical studies.

Time Trends of Greenspaces, Air Pollution, and Asthma Prevalence among Children and Adolescents in India.

The prevalence of childhood asthma contributes to the global burden of the disease substantially. Air pollution in India has increased. In this study, we examine the associations among greenspaces, air pollution, and asthma prevalence in children and adolescents over a large, diverse population in India. We used state-wide global burden of disease data on asthma from age 0 to 19 years in 2005, 2011, and 2017. For greenspace, we used the normalized differential vegetation index (NDVI), which is the surface reflectance of light during photosynthetic activity. NDVI, air pollutants (PM2.5, PM10, SO2, NO2, and O3), weather, and socio-demographic factors were included in generalized estimating equation (GEE) models to estimate their associations with childhood asthma prevalence over time. Novel data visualization illustrated the complex spatial distributions. NDVI was associated with asthma prevalence (ß = 0.144; 95% CI = 0.10, 0.186; p < 0.0001) for high PM2.5, along with high levels of both gaseous air pollutants, SO2, and NO2 ((ß = 0.12; 95% CI = 0.08, 0.16; p < 0.0001) and (ß = 0.09; 95% CI = 0.05, 0.13; p < 0.0001)). However, NDVI and high O3, had a strong negative association with asthma prevalence (ß = -0.19; 95% CI = -0.26, -0.11; p < 0.0001). We observed additional effects of the interaction between the NDVI and high concentrations of PM2.5, PM10, NO2, and O3, assuming that these associations share a common pathway, and found interaction effects for asthma prevalence. Given the changing environmental conditions that interplay over geographical characteristics on the prevalence of asthma, further studies may elucidate a better understanding of these complex associations.

Association of Serum Albumin and Copeptin with Early Clinical Deterioration and Instability in Community-Acquired Pneumonia.

Background: There is a paucity of data on biomarkers for the early deterioration and clinical instability of patients in community-acquired pneumonia (CAP), as treatment failure occurs in the first seven days in 90% of patients. Aim: To evaluate serum albumin and copeptin with CURB-65, PSI scoring and ATS/IDSA minor criteria for the prediction of early mortality or ICU-admission (7 days) and clinical instability after 72 h. Methods: In 100 consecutive hospitalized adult CAP patients, PSI-scores, CURB-65 scores, ATS/IDSA 2007 minor criteria, copeptin and albumin on admission were evaluated. Univariate and multivariate Cox regression analysis was performed to assess independent risk factors for early combined mortality or ICU admission. Predictive powers of albumin and copeptin were tested with ROC curves and ICU-free survival probability was tested using Kaplan−Meier analysis. Results: Albumin was lower and copeptin higher in patients with short-term adverse outcomes (p < 0.05). Cox regression analysis showed that albumin [HR (95% CI): 0.41 (0.18−0.94, p = 0.034)] and copeptin [HR (95% CI): 1.94 (1.03−3.67, p = 0.042)] were independent risk factors for early combined mortality or ICU admission (7 days). The Kaplan−Meier analysis observed that high copeptin (>27.12 ng/mL) and low albumin levels (<2.85 g/dL) had a lower (p < 0.001) survival probability. The diagnostic accuracy of albumin was better than copeptin. The inclusion of albumin and copeptin into ATS/IDSA minor criteria significantly improved their predictive power. Conclusions: Both biomarkers serum albumin and copeptin can predict early deterioration and clinical instability in hospitalized CAP patients and increase the prognostic power of the traditional clinical scoring systems.

The Role of Neutrophil-to-Lymphocyte Ratio in Risk Stratification and Prognostication of COVID-19: A Systematic Review and Meta-Analysis.

Several studies have proposed that the neutrophil−lymphocyte ratio (NLR) is one of the various biomarkers that can be useful in assessing COVID-19 disease-related outcomes. Our systematic review analyzes the relationship between on-admission NLR values and COVID-19 severity and mortality. Six different severity criteria were used. A search of the literature in various databases was conducted from 1 January 2020 to 1 May 2021. We calculated the pooled standardized mean difference (SMD) for the collected NLR values. A meta-regression analysis was performed, looking at the length of hospitalization and other probable confounders, such as age, gender, and comorbidities. A total of sixty-four studies were considered, which included a total of 15,683 patients. The meta-analysis showed an SMD of 3.12 (95% CI: 2.64−3.59) in NLR values between severe and non-severe patients. A difference of 3.93 (95% CI: 2.35−5.50) was found between survivors and non-survivors of the disease. Upon summary receiver operating characteristics analysis, NLR showed 80.2% (95% CI: 74.0−85.2%) sensitivity and 75.8% (95% CI: 71.3−79.9%) specificity for the prediction of severity and 78.8% (95% CI: 73.5−83.2%) sensitivity and 73.0% (95% CI: 68.4−77.1%) specificity for mortality, and was not influenced by age, gender, or co-morbid conditions. Conclusion: On admission, NLR predicts both severity and mortality in COVID-19 patients, and an NLR > 6.5 is associated with significantly greater the odds of mortality.

Impact of Acute Exacerbation and Its Phenotypes on the Clinical Outcomes of Chronic Obstructive Pulmonary Disease in Hospitalized Patients: A Cross-Sectional Study.

Acute exacerbations of COPD (AECOPD) are clinically significant events having therapeutic and prognostic consequences. However, there is a lot of variation in its clinical manifestations described by phenotypes. The phenotypes of AECOPD were categorized in this study based on pathology and exposure. In our cross-sectional study, conducted between 1 January 2016 to 31 December 2020, the patients were categorized into six groups based on pathology: non-bacterial and non-eosinophilic; bacterial; eosinophilic; bacterial infection with eosinophilia; pneumonia; and bronchiectasis. Further, four groups were classified based on exposure to tobacco smoke (TS), biomass smoke (BMS), both, or no exposure. Cox proportional-hazards regression analyses were performed to assess hazard ratios, and Kaplan-Meier analysis was performed to assess survival, which was then compared using the log-rank test. The odds ratio (OR) and independent predictors of ward admission type and length of hospital stay were assessed using binomial logistic regression analyses. Of the 2236 subjects, 2194 were selected. The median age of the cohort was 67.0 (60.0 to 74.0) and 75.2% were males. Mortality rates were higher in females than in males (6.2% vs. 2.3%). AECOPD-B (bacterial infection) subjects [HR 95% CI 6.42 (3.06-13.46)], followed by AECOPD-P (pneumonia) subjects [HR (95% CI: 4.33 (2.01-9.30)], were at higher mortality risk and had a more extended hospital stay (6.0 (4.0 to 9.5) days; 6.0 (4.0 to 10.0). Subjects with TS and BMS-AECOPD [HR 95% CI 7.24 (1.53-34.29)], followed by BMS-AECOPD [HR 95% CI 5.28 (2.46-11.35)], had higher mortality risk. Different phenotypes have different impacts on AECOPD clinical outcomes. A better understanding of AECOPD phenotypes could contribute to developing an algorithm for the precise management of different phenotypes.

Circulating Secretoglobin Family 1A Member 1 (SCGB1A1) Levels as a Marker of Biomass Smoke Induced Chronic Obstructive Pulmonary Disease.

Secretoglobin family 1A member 1 (SCGB1A1) alternatively known as club cell protein 16 is a protective pneumo-protein. Decreased serum levels of SCGB1A1 have been associated with tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD). Exposure to biomass smoke (BMS) is an important COPD risk factor among women in low and lower-middle income countries. Therefore, in a cross-sectional study (n = 50/group; total 200 subjects) we assessed serum SCGB1A1 levels in BMS-COPD subjects (11 male, 39 female) compared to TS-COPD (all male) along with TS-CONTROL (asymptomatic smokers, all male) and healthy controls (29 male, 21 female) in an Indian population. Normal and chronic bronchitis like bronchial mucosa models developed at the air-liquid interface using human primary bronchial epithelial cells (3 donors, and three replicates per donor) were exposed to cigarette smoke condensate (CSC; 0.25, 0.5, and 1%) to assess SCGB1A1 transcript expression and protein secretion. Significantly (p < 0.0001) decreased serum SCGB1A1 concentrations (median, interquartile range, ng/mL) were detected in both BMS-COPD (1.6; 1.3-2.4) and TS-COPD (1.8; 1.4-2.5) subjects compared to TS-CONTROL (3.3; 2.9-3.5) and healthy controls (5.1; 4.5-7.2). The levels of SCGB1A1 were positively correlated (r = 0.7-0.8; p < 0.0001) with forced expiratory volume in 1 s, forced vital capacity, their ratios, and exercise capacity. The findings are also consistent within the BMS-COPD sub-group as well. Significantly (p < 0.03) decreased SCGB1A1 concentrations were detected with severity of COPD, dyspnea, quality of life, and mortality indicators. In vitro studies demonstrated significantly (p < 0.05) decreased SCGB1A1 transcript and/or protein levels following CSC exposure. Circulating SCGB1A1 levels may therefore also be considered as a potent marker of BMS-COPD and warrant studies in larger independent cohorts.

Putative Systemic Biomarkers of Biomass Smoke-Induced Chronic Obstructive Pulmonary Disease among Women in a Rural South Indian Population.

RATIONALE: Exposure to biomass smoke (BMS) has been implicated in chronic obstructive pulmonary disease (COPD). About 3 billion people worldwide use biomass fuel for cooking and heating. Women in rural communities of low- and lower-middle-income countries are disproportionately exposed to massive amounts of BMS during active cooking hours (4-6 h/day). Therefore, BMS exposure is considered as a risk factor for COPD in the same order of magnitude as tobacco smoke. In rural India, due to cultural reasons, women are the primary cook of the family and are mostly nonsmokers. Thus, BMS-induced COPD is predominant among rural Indian women. However, BMS-COPD remains a relatively unexplored health problem globally. Therefore, we investigated the serum chemokine and cytokine signatures of BMS-COPD and tobacco smoke-induced COPD (TS-COPD) patients compared to their control in a rural South Indian population for this field study. METHODS: Concentrations of 40 serum chemokines and cytokines were measured using a multiplexed immunoassay. The study cohort consisted of BMS-COPD (female; n = 29) and BMS-exposed subjects without COPD (BMS-CONTROL; female; n = 24). For comparison, data from TS-COPD patients (male, n = 23) and tobacco smokers without COPD (TS-CONTROL; male, n = 22) were investigated. Subjects were matched for age, sex, and biomass exposure. Tobacco consumption was slightly higher in TS-COPD subjects compared to TS-CONTROL. BMS-exposed and TS-exposed subjects (currently exposed) were from the same locality with similar dwelling habits and socioeconomic status. A validated structured questionnaire-based survey and spirometry was performed. An additional control group with no tobacco and BMS exposure (TS-BMS-CONTROL; n = 15) was included. Statistical significance was set at p ≤ 0.01. RESULTS: Serum median concentrations (pg/ml) of CCL15 [8799.35; 5977.22], CCL27 [1409.14; 1024.99], and CXCL13 [37.14; 26.03] were significantly higher in BMS-CONTROL compared to BMS-COPD subjects. Nine analytes exhibited higher concentrations in TS-CONTROL compared to TS-COPD subjects. Comparison of chemokine and cytokine concentrations among BMS-COPD versus TS-COPD and BMS-CONTROL versus TS-CONTROL subjects also revealed distinct molecular signatures. CONCLUSION: Our data identifies CCL27 and CXCL13 as putative, plausibly homeostatic/protective biomarkers for BMS-COPD within the investigated population that warrants validation in larger and multiple cohorts. The findings further indicate exposure-specific systemic response of chemokines and cytokines.

Association of Elevated Serum GM-CSF, IFN-γ, IL-4, and TNF-α Concentration with Tobacco Smoke Induced Chronic Obstructive Pulmonary Disease in a South Indian Population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a devastating condition with limited pharmacotherapeutic options and exceptionally high public-health burden globally as well as in India. Tobacco smoking is the primary cause for COPD among men in India. Systemic inflammation involving altered regulation of cytokines controlling the host defense mechanism is a hallmark of COPD pathogenesis. However, biomarker discovery studies are limited among Indian COPD patients. METHODS: We assessed the serum concentrations [median (25th-75th percentile) pg/ml] of interleukin (IL)-2,4,6,8,10, granulocyte macrophage colony stimulating factor (GM-CSF), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) using a multiplexed immunoassay. Our study cohort consisted of 30 tobacco smokers with COPD (TS COPD) and 20 tobacco smokers without COPD (TS CONTROL) from South India. The study population was matched for age, sex (male), and tobacco consumption (pack-years). COPD was diagnosed according to the global initiative for chronic obstructive lung disease (GOLD) criteria of persistent airflow obstruction determined by the ratio of postbronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of <0.7. A validated structured questionnaire-based survey [Burden of Obstructive Lung Disease (BOLD) study] and spirometry were performed during house to house visit of the field study. Statistical analysis included nonparametric (two-tailed) Mann-Whitney U and Spearman rank test, as appropriate (significance: p<0.05). RESULTS: Serum GM-CSF [69.64 (46.67, 97.48); 36.78 (30.07, 53.88), p=0.014], IFN-γ [51.06 (17.00, 84.86); 11.70 (3.18, 32.81), p=0.017], IL-4 [9.09 (1.8, 19.9); 1.8 (1.8, 4.46); p=0.024], and TNF-α [20.68 (5.5, 29.26); 3.5 (3.5, 4.5); p<0.001] concentrations (pg/ml) were increased in TS COPD subjects compared to TS CONTROL. A weak correlation between lung function parameters and cytokine concentrations was detected. CONCLUSION: Our pilot study reveals GM-CSF, IFN-γ, IL-4, and TNF-α as plausible COPD susceptibility biomarkers within the investigated South Indian population that needs to be validated in a larger cohort.