GOLD Stage Research Articles

TEST-RETEST RELIABILITY OF THE ST. GEORGE’S RESPIRATORY QUESTIONNAIRE IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) PATIENTS: A SYSTEMATIC REVIEW.

Background: The St. George's Respiratory Questionnaire (SGRQ) is an established tool for assessing health-related quality of life (HRQoL) in patients with Chronic Obstructive Pulmonary Disease (COPD). However, the reliability of this tool, particularly its test-retest reliability across different populations, has shown varying results. Objective: This systematic review aims to evaluate the test-retest reliability of the SGRQ across different studies involving COPD patients and analyzing its consistency in different settings and patient groups. Methods: A comprehensive search of electronic databases, including PubMed, Web of Science, and Scopus, adhering to PRISMA guidelines, identified 8 eligible studies involving 534 COPD patients across various countries and healthcare settings. Data were extracted on study design, patient demographics, disease severity (GOLD stages I-IV), and SGRQ administration. Test-retest reliability was evaluated using intraclass correlation coefficients (ICCs) and statistical significance was assessed using p-values. Results: The SGRQ showed moderate to strong test-retest reliability across studies, with ICC values ranging from 0.54 to 0.98, indicating stability over time. Most studies reported reliability across all GOLD stages of COPD, from stable to acute exacerbations. COSMIN quality assessments showed excellent stability in some studies, though inconsistencies were found, particularly in the symptom subscales. Conclusion: The SGRQ demonstrates strong test-retest reliability for assessing HRQoL in COPD patients. However, variability in the symptom subscale suggests further research is needed across diverse populations and healthcare settings.

Risk factors for renal progression in patients with CKD and coexisting COPD.

Chronic diseases rarely occur in isolation, and chronic kidney disease (CKD) is no exception. There has been considerable research on the interplay between the heart and kidneys, but studies on the relationship between the lungs and kidneys are less common. The interaction between pulmonary and renal functions in areas such as acid-base metabolism, chronic inflammation, and bone metabolism is increasingly gaining clinical attention. In this cohort study, we examined 480 patients with stages 3-4 CKD and COPD (GOLD stages 1 and 2) to identify risk factors that contribute to the progression of renal function to a composite endpoint, which includes a 40% decline in estimated glomerular filtration rate (eGFR) and the onset of end-stage renal disease during follow-up periods. A Cox proportional hazards regression model was used to investigate the risk factors associated with the timing of renal event endpoints in the study population. Additionally, the restricted cubic spline method was used to explore the relationship between quantitative variables and survival risk. Our study included 480 eligible patients with an average follow-up period of 21.41 ± 14.90months, during which 224 individuals (46.7%) experienced the composite renal endpoints. Multivariable Cox regression analysis revealed that systolic blood pressure (SBP) [1.01 (1.00-1.02), p = 0.002], hemoglobin (Hb) [HR 0.89 (0.83-0.96), p = 0.002], albumin (Alb) [0.96 (0.93-0.99), p = 0.009], and edema [1.73 (1.29-2.33), p < 0.001] were independent risk factors for the renal endpoints. The adjusted multivariable Cox regression analysis demonstrated that elevated SBP and edema were factors that promoted the occurrence of composite endpoints, while higher levels of Hb and Alb were protective factors.

The Effect of the Severity of Chronic Obstructive Pulmonary Disease on the Pituitary Gonadal Axis

This study aims to investigate the levels of anabolic hormone implicated in specific clinical symptoms of chronic obstructive pulmonary disease (COPD) in relation to disease severity. Sixty-four male patients with COPD for at least two years were included. COPD diagnosed was based on pulmonary function tests, with severity classified using the CAT score and mMRC breathlessness scale. Levels of various hormones including TSH T3 T4, FSH, LH, testesterone, prolactin, progesterone and CRP were measured. Arterial blood gases were also analyzed. Patients were categorized according to GOLD stages. LH, FSH levels decreased during exacerbation, with a significant positive correlation between LH and low arterial oxygen levels. lower testosterone levels were statistically significant in severe COPD patients with FEV1 &lt; 50%. A decrease in LH, testosterone FSH, TSH, progesterone and prolactin was observed with low blood oxygen levels, indicating dysfunction in the hypothalamic-pituitary-gonadal axis. However,stastistical significance varied.In conclusion, hormonal changes occur in male COPD patients, particulary related to disease severity. Testesterone levels correlate significantly with COPD severity. LH decrease during pronounced hypoxemia period was notable. Further research is necessary to evaluate the safety and efficacy of testosterone supplementation in COPD patients.

Prevalence of systemic hypertension in COPD patients with GOLD stage 1 disease

Morbidity and death in COPD patients is greatly influenced by co morbidities. We aim to study the prevalence of systemic hypertension in the initial stages of COPD, i.e. in patients with GOLD stage 1 disease having a FEV1 greater than 80% of predicted value in PFT. We conducted a period prevalence study on patients with early stages of COPD. Patients were evaluated for systemic hypertension after being diagnosed with COPD by pulmonary function test. The study was conducted at Sri Venkateswaraa Medical College Hospital and Research Institute, Chennai. A total of 205 patients were identified with COPD meeting the necessary inclusion and exclusion criteria. 150 patients were male and 55 were female. Among them 53.6% patients were diagnosed with systemic hypertension. 20.9% of the hypertensive patients were having obesity. 95.4% of the patients with hypertension were tobacco smokers. 4.6% of the patients with hypertension were having a history of biomass fuel smoke exposure. Tobacco smoking, biomass fuel smoke exposure and obesity are important factors which influence lung function and many cardiovascular/cerebrovascular diseases. Patients in the early stages of COPD have a higher prevalence of systemic hypertension. Systemic hypertension must be identified and treated early to prevent long term cardiovascular/cerebrovascular complications in COPD patients.

Airway Tapering in Chronic Obstructive Pulmonary Disease.

Luminal narrowing is a hallmark feature of airway remodeling in COPD, but current measures focus on airway wall remodeling. Quantification of the natural increase in cumulative cross-sectional area along the length of the human airway tree can facilitate assessment of airway narrowing. We analysed the airway trees of 7641 subjects enrolled in the multicenter COPDGene cohort. Airway luminal tapering was assessed by estimating the slope of the change in cumulative cross-sectional area along the length of the airway tree over successive generations (T-Slope). We performed multivariable regression analyses to test the associations between T-Slope and lung function, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea score, 6-minute walk distance (6 MWD), FEV1 change, exacerbations, and all-cause mortality after adjusting for demographics, %CT emphysema, and total airway count. The T-Slope decreased with increasing COPD severity: 2.69 (0.70) in nonsmokers and 2.33 (0.70), 2.11 (0.65), 1.78 (0.58), 1.60 (0.53), and 1.57 (0.52) in GOLD stages 0 through 4 respectively (Jonckheere-Terpstra p=0.04). On multivariable analyses, the T-Slope was independently associated with FEV1 (β=0.13 L, 95% CI 0.10 to 0.15, p<0.001), 6MWD (β=15.0 m, 95%CI 10.8 to 19.2, p<0.001), change in FEV1 (β=-4.50 ml·year-1, 95% CI -7.32 to -1.67; p=0.001), exacerbations (IRR=0.78, 95% CI 0.73 to 0.83, p<0.001), and mortality (HR=0.79, 95% CI 0.72 to 0.86, p<0.001). T-Slope is a measure of airway luminal remodeling and is associated with respiratory morbidity and mortality.

Efficacy of respiratory support therapies during pulmonary rehabilitation exercise training in chronic obstructive pulmonary disease patients: a systematic review and network meta-analysis

BackgroundExercise training is fundamental in pulmonary rehabilitation (PR), but patients with chronic obstructive pulmonary disease (COPD) often struggle with exercise intolerance. Respiratory support during exercise in COPD patients may be a beneficial adjunct therapy. In this study, the effect of different respiratory support therapy during pulmonary rehabilitation exercise training in COPD patients was assessed through a network meta-analysis.MethodsFive databases were searched to obtain randomized controlled trials involving different respiratory support therapies during PR exercise training in COPD patients. The Cochrane Handbook tool was employed to assess the risk bias of included studies. Network meta-analysis was performed using the STATA software. The study protocol was registered at PROSPERO (CRD42023491139).ResultsA total of 35 studies involving 1321 patients and 6 different interventions were included. Network meta-analysis showed that noninvasive positive pressure ventilation (NPPV) is superior in improving exercise capacity (6-Minute Walk Test distance, peak work rate, endurance time), dyspnea, and physiological change (peak VO2, tidal volume, minute ventilation and lactate level) in stable COPD patients who were at GOLD stage III or IV during PR exercise training. The final surface under the cumulative ranking curve value indicated that NPPV therapy achieved the best assistive rehabilitation effect.ConclusionsThe obtained results indicate that NPPV is most powerful in assisting exercise in severe COPD patients under stable condition. Researchers should focus more on the safety, feasibility, and personalization of interventions. Furthermore, there is a need for additional high-quality trials to assess the consistency of evidence across various respiratory support approaches.Trial registrationThe study was registered at PROSPERO (CRD42023491139).

The influence of CLEC5A on early macrophage-mediated inflammation in COPD progression

Chronic obstructive pulmonary disease (COPD) is a complex syndrome with poorly understood mechanisms driving its early progression (GOLD stages 1–2). Elucidating the genetic factors that influence early-stage COPD, particularly those related to airway inflammation and remodeling, is crucial. This study analyzed lung tissue sequencing data from patients with early-stage COPD (GSE47460) and smoke-exposed mice. We employed Weighted Gene Co-Expression Network Analysis (WGCNA) and machine learning to identify potentially pathogenic genes. Further analyses included single-cell sequencing from both mice and COPD patients to pinpoint gene expression in specific cell types. Cell–cell communication and pseudotemporal analyses were conducted, with findings validated in smoke-exposed mice. Additionally, Mendelian randomization (MR) was used to confirm the association between candidate genes and lung function/COPD. Finally, functional validation was performed in vitro using cell cultures. Machine learning analysis of 30 differentially expressed genes identified 8 key genes, with CLEC5A emerging as a potential pathogenic factor in early-stage COPD. Bioinformatics analyses suggested a role for CLEC5A in macrophage-mediated inflammation during COPD. Two-sample Mendelian randomization linked CLEC5A single nucleotide polymorphisms (SNPs) with Forced Expiratory Volume in One Second (FEV1), FEV1/Forced Vital Capacity (FVC) and early/later on COPD. In vitro, the knockdown of CLEC5A led to a reduction in inflammatory markers within macrophages. Our study identifies CLEC5A as a critical gene in early-stage COPD, contributing to its pathogenesis through pro-inflammatory mechanisms. This discovery offers valuable insights for developing early diagnosis and treatment strategies for COPD and highlights CLEC5A as a promising target for further investigation.

Telluride Mineralogy of the Kochbulak Epithermal Gold Deposit, Tien Shan, Eastern Uzbekistan

The Kochbulak gold deposit is situated on the northern slope of the Kurama range of eastern Uzbekistan and is one of the largest Tellurium-rich epithermal gold deposits in the world. Based on a detailed field and petrological investigation, three stages of mineralization can be classified, including, from early to late, quartz–pyrite vein stage, quartz–telluride–sulfide–sulphosalt–native gold stage, and pyrite–chalcopyrite vein stage. Abundant tellurides, including tellurobismuthite, rucklidgeite, tetradymite, altaite, volynskite, and hessite, have been well recognized in the second (main) mineralization stage. Based on the mineral assemblages and petrogenetic occurrence, the sequence of tellurides in the second mineralization stage can be approximately identified as altaite+calaverite+native tellurium, calaverite+native gold, Bi-telluride (e.g., tellurobismuthite and rucklidgeite)+petzite+native gold, Ag-Bi telluride (e.g., volynskite), and Ag-telluride (e.g., hessite)+native gold. By depicting the Log ƒ(Te2)-Log ƒ(S2) relationship diagram of the Kochbulak gold deposit under 250 °C and 200 °C, the Log ƒ(S2) value ranges from −14.7 to −8.6 and from −16.7 to −10.9, respectively, with Log ƒ(Te2) value varies from −12.3 to −7.8 under 250 °C and ranges from −13.8 to −11.2 under 200 °C.

Smoking-Dependent Association of Serum Brain-Derived Neurotrophic Factor with Pulmonary Function Parameters in Chronic Obstructive Pulmonary Disease.

Background and Objectives: One of the members of the neurotrophin (NT) family is the brain-derived neurotrophic factor (BDNF). In addition to its role in the nerve system, it has been found to play a role in lung health and diseases. Materials and Methods: The serum concentrations of BDNF were assessed in 57 patients with COPD and in 19 control individuals and the possible associations of BDNF with the spirometric indexes and disease stages were explored. Results: We did not find a significant difference between the serum concentrations of BDNF of patients and controls (p = 0.521). A significant negative correlation of the serum BDNF levels with the age of the patients (Rho = -0.279, p = 0.036) was observed. In addition, a borderline negative correlation with the age of disease onset (Rho= -0.244, p = 0.063) was also found. When analyzing these correlations in different genders, we found stronger statistical significance in male patients (Rho = -0.398, p = 0.009; and Rho = -0.419, p = 0.006), while no such significance was found in females (p = 0.574 and p = 0.342). The analyses of the possible relations of serum BDNF concentration with the spirometric parameters in the whole group of patients did not reveal any significance (p = 0.231 for FEV1%pr. and p = 0.271 for FEV1/FVC%). However, when the patients were dichotomized on the basis of smoking habits, we obtained a strong positive correlation between BDNF and FEV1%pr. (Rho = 0.501, p = 0.048) in non-smokers, but strong negative correlations with FEV1%pr. (Rho = -0.468, p = 0.003) and with FEV1/FVC% (Rho = -0.331, p = 0.040) in ex/current smokers. Non-smokers with moderate disease (GOLD II) had higher BDNF serum concentrations than patients with GOLD stage III/IV (p = 0.031). In ex/current smokers, there was an opposite association (p = 0.045). Conclusions: The results of our study suggest that the expression and secretion of BDNF are changed in COPD, but its effects and functions may differ according to the smoking history of the patients.

Clinical Significance of Long Non-Coding RNA SNHG5 in the Diagnosis and Prognosis of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is preventable and requires early screening. The study aimed to examine the clinical values of long non-coding RNA (lncRNA) SNHG5 in COPD diagnosis and prognosis. Out of 160 COPD patients, 80 were in the stable stage and 80 were in the acute exacerbation of COPD stage (AECOPD). SNHG5 expression was detected via qRT-PCR. The survival analysis was conducted using Cox regression analysis and K-M curve. SNHG5 levels significantly reduced in both stable COPD and AECOPD groups compared with the control group, with AECOPD group recording the lowest values. SNHG5 levels were negatively correlated with GOLD stage. Serum SNHG5 can differentiate stable COPD patients from healthy individuals (AUC = 0.805), and can screen AECOPD from stable ones (AUC = 0.910). SNHG5 negatively influenced the release of inflammatory cytokines. For AECOPD patients, those with severe cough and wheezing dyspnea symptoms exhibited the lowest values of SNUG5. Among the 80 AECOPD patients, 16 cases died in the one-year follow-up, all of whom had low levels of SNHG5. SNHG5 levels independently influenced survival outcomes, patients with low SNHG5 levels had a poor prognosis. Thus, lncRNA SNHG5, which is downregulated in patients with COPD (especially AECOPD), can potentially protect against AECOPD and serve as a novel prognostic biomarker for AECOPD.

Two stages of gold mineralization in the Hebaoshan deposit: Evidence from the U-Pb dating and trace element geochemistry of rutile, monazite and apatite

The Hebaoshan gold deposit (41.5 t Au @ 3.5 g/t) is located in the southeastern region of the South China Block, central part of the Wuyishan metallogenic belt. The ore-hosting rocks in this area are predominantly Precambrian metasedimentary rocks and Caledonian granitic rocks. Two hydrothermal mineralization stages can be distinguished: a quartz-sericite-pyrite-native gold (stage I) and a chlorite-quartz-sericite-chalcopyrite-electrum (stage II), with hydrothermal monazite and rutile are firstly identified in separate stages. The complex geological history of the region has resulted in ongoing debates regarding the age of gold mineralization and the genesis of the major gold deposits in this area. In order to precisely constrain the mineralization age of the deposit and further establish a genetic model for the ore deposit, LA-ICP-MS U-Pb dating and trace element analysis on accessory minerals were conducted. Based on the textures mineral assemblages, and geochemical features of the accessory minerals, magmatic apatite, hydrothermal rutile, and both magmatic and hydrothermal monazite were identified. The U-Pb ages of magmatic apatite and monazite are determined to be 445.3 ± 15.80, 441.3 ± 15.10 Ma and 446.57 ± 1.03 Ma, respectively, suggesting that these ages represent the emplacement ages of the Caledonian intrusive rocks. The ages of hydrothermal monazite and hydrothermal rutile are determined to be 238.46 ± 2.01 Ma (single-mineral analysis), 238.46 ± 2.01 Ma (in-suit analysis) and 179.54 ± 7.28 Ma, respectively, suggesting that represent two mineralization events during the Late Triassic to early Jurassic in the Hebaoshan area. These data provide new constraints on the mineralization process in the Hebaoshan deposit and excludes the link between gold mineralization and the intrusion of the Caledonian granites. Regionally, It is speculated that the two mineralization events at Hebaoshan are respectively associated with intracontinental orogenic movements between the Yangtze Block and Cathaysia Block, the flat-slab subduction of the Paleo-Pacific Plate (stage I), and the subsequent extensional tectonics related to the collision between the Yangtze Block and Cathaysia Block (stage II).Our study indicates that the timing of multiple episodic mineralization can be constrained by analysis of accessory minerals, which provides a geological basis for better genetic model for the deposit and provide geological evidence for unraveling the relationships between magmatic activities and mineralization events in the region.

Evaluating the clinical utility of small airway function assessment for early diagnosis of GOLD stage 0 chronic obstructive pulmonary disease

Objective To investigate the clinical utility of small airway function indices for early identification of GOLD stage 0 chronic obstructive pulmonary disease (COPD). Methods This retrospective study enrolled 137 participants at our institution between January 2017 and December 2018, comprising 40 healthy controls, 46 individuals with GOLD stage 0 COPD, and 51 patients with established COPD. Pulmonary function was assessed using the PowerCube spirometry system (GANSHORN, Germany). Parameters evaluated included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and small airway function indicators. Results The COPD cohort exhibited significantly lower values across all lung function measures compared to the other two groups, particularly for dynamic lung volume parameters such as FEV1%predicted and FEV1/FVC%. Small airway function indices, including FEV3%predicted, FEF75%predicted, FEF50%predicted, FEF25%predicted, and MMEF%predicted, were markedly decreased in the COPD group (all p-values <0.001). Receiver operating characteristic (ROC) curve analysis demonstrated that MMEF/FVC% and FEV3/FVC% had high diagnostic accuracy for COPD, with MMEF/FVC% exhibiting the optimal sensitivity and specificity. Conclusion Small airway function indices, especially MMEF/FVC%, can serve as effective tools for early identification of GOLD stage 0 COPD. Incorporation of these findings into clinical practice may facilitate early diagnosis and intervention, thereby improving treatment outcomes and patient quality of life.

Cardiorespiratory Effects of Tai Chi Versus Walking: Exploratory Data from the LEAP Trial

ABSTRACT Background: Tai Chi (TC), a mind-body exercise, may be a potential exercise maintenance strategy for patients with chronic obstructive pulmonary disease (COPD) after pulmonary rehabilitation. We sought to characterize the acute cardiorespiratory response during TC versus walking in patients with COPD after a 24-week intervention. Methods: Cardiorespiratory data were available on 26 adults with COPD (46% female, 54% GOLD stage III–IV) randomized to TC (n = 19) or group walking (n = 7). At 24 weeks, we examined between-groups standard cardiorespiratory measures (heart rate (HR), oxygen consumption (VO2), expired carbon dioxide (VCO2), respiratory rate (RR), and ventilation (VE)) during a multiphase in-class characterization protocol. Continuous HR data during resting and exercise phases were analyzed for time- and frequency-domain HR variability (HRV) indices. Results: At 24 weeks, during exercise phases, those in TC exhibited a mean HR of 80 ± 15 b · min−1, RR of 16.5 ± 4 breaths·min−1, and VO2 of 434.8 ± 146.5 mL·min−1; and in walking 95.7 ± 9.2 b·min −1, 26.2 ± 8 breaths·min−1, and 901.3 ± 261.2 mL·min−1, respectively (P &amp;lt; 0.05). Overall, TC was less strenuous with lower HR, VO2, VCO2, RR, and VE (P &amp;lt; 0.05). At rest, TC demonstrated more favorable respiratory efficiency (VE/VCO2; 35.53 ± 5.65 versus 41.07 ± 5.21, P &amp;lt; 0.05). During the postexercise recovery phase, time-domain HRV indices decreased after walking (e.g., pNN20: 35.7 ± 24.1 baseline, 10.3 ± 9.5 postwalk; pNN50: 20.9 ± 18.5 baseline, 3.9 ± 3.7 postwalk), while they remained relatively unchanged after TC. Frequency-domain HRV measures suggested greater total power (TP) across all phases of TC versus walking, particularly during meditation (P &amp;lt; 0.05 for LnTP). Conclusion: Preliminary data support that TC may be associated with improved pulmonary efficiency and reduced rapid shallow breathing compared with walking and be a viable exercise maintenance option after pulmonary rehabilitation.

PREVALENCE AND CORRELATION OF METABOLIC SYNDROME IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Background: Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are prevalent chronic conditions with significant impacts on public health. Despite evidence suggesting a bidirectional relationship between COPD and MetS, data on the prevalence and correlation of MetS in COPD patients remain limited.This cross-sectional study aimed to investigate the prevalence of MetS in COPD patients admitted at Rural Medical College Loni and explore its correlation. Methods: A total of 50 COPD patients aged 40 years and above were recruited. Demographic and clinical data were collected through face-to-face interviews and medical record review. Diagnosis ofMetS was done based on the International Diabetes Federation criteria. Logistic regression analysis was performed to identify factors associated with MetS in COPD patients. Results: The mean age of the study population was 60.92 ± 8.97 years, with 76% being male. The prevalence of MetS among COPD patients was42%. The majority of patients with MetS exhibited grade 3 dyspnea based on modified medical research council grading (MMRC). MetS was most prevalent among patients with GOLD stage III disease. Conclusion: Metabolic syndrome is highly prevalent among COPD patientsadmitted at Rural Medical College Loni andpatients with MetS present with more severe disease and frequent exacerbations. Identification of MetS in COPD patients is crucial for comprehensive disease management and warrants integrated care approaches targeting both respiratory and metabolic health. Further research is needed to elucidate the underlying mechanisms linking COPD and MetS and develop tailored interventions to improve outcomes in this population.

Defining the role of exertional hypoxemia and pulmonary vasoconstriction on lung function decline, morbidity, and mortality in patients with chronic obstructive lung disease – the PROSA study: rationale and study design

BackgroundChronic obstructive lung disease (COPD) has diverse molecular pathomechanisms and clinical courses which, however, are not fully mirrored by current therapy. Intermittent hypoxemia is a driver of lung function decline and poor outcome, e.g., in patients with concomitant obstructive sleep apnea. Transient hypoxemia during physical exercise has been suggested to act in a similar manner. The PROSA study is designed to prospectively assess whether the clinical course of COPD patients with or without exertional desaturation differs, and to address potential pathophysiological mechanisms and biomarkers.Methods148 COPD patients (GOLD stage 2–3, groups B or C) will undergo exercise testing with continuous pulse oximetry. They will be followed for 36 months by spirometry, echocardiography, endothelial function testing, and biomarker analyses. Exercise testing will be performed by comparing the 6-min walk test (6MWT), bicycle ergometry, and a 15-sec breath-hold test. Exertional desaturation will be defined as SpO2 < 90% or delta-SpO2 ≥ 4% during the 6MWT. The primary endpoint will be the rate of decline of FEV1(LLN) between COPD patients with and without exertional desaturation.DiscussionThe PROSA Study is an investigator-initiated prospective study that was designed to prove or dismiss the hypothesis that COPD patients with exertional desaturation have a significantly more rapid rate of decline of lung function as compared to non-desaturators. A 20% difference in the primary endpoint was considered clinically significant; it can be detected with a power of 90%. If the primary endpoint will be met, exercise testing with continuous pulse oximetry can be used as a ubiquitously available, easy screening tool to prospectively assess the risk of rapid lung function decline in COPD patients at an early disease stage. This will allow to introduce personalized, risk-adapted therapy to improve COPD outcome in the long run. PROSA is exclusively funded by public funds provided by the European Research Council through an ERC Advanced Grant. Patient recruitment is ongoing; the PROSA results are expected to be available in 2028.Trial registrationThe PROSA Study has been prospectively registered at clinicaltrials.gov (register no. NCT06265623, dated 09.02.2024).

Telerehabilitation of Chronic Obstructive Pulmonary Disease Patients in a Tertiary Care Hospital in Western India: A 3-month Follow-up Study

Abstract Introduction: India grapples with a mounting chronic obstructive pulmonary disease (COPD) crisis driven by pervasive air pollution, especially from biomass burning. New Delhi’s classification as the capital with the worst pollution, with 35 other Indian cities in the global top 50, underscores the severity. COPD, the third-leading cause of global mortality, claimed 3.23 million lives in 2019, with a projected surge due to prevalent smoking and ongoing pollution. Domestically, COPD accounts for 9.5% of all deaths. Emphasizing the urgency of Sustainable Development Goal 3.4 to reduce mortality from non-communicable diseases, including chronic respiratory diseases, cost-effective pulmonary rehabilitation (PR), particularly telerehabilitation, emerges as a promising avenue for comprehensive COPD management in this challenging landscape. Methods: Patients with COPD (gold stages 1–3) confirmed by pulmonary function tests were enrolled. Functional exercise capacity, dyspnoea levels and health-related quality of life (HRQoL) were assessed using the 6-min walk test (6MWD), modified Medical Research Council (mMRC) dyspnoea scale and SGRQ-C questionnaire, respectively. Participants received home-based PR and attended one 2-h PR session 3 days a week for 12 weeks. Follow-up was conducted telephonically monthly, and a final assessment was done at the end of the 3rd month. Results: Of the 88 initially recruited patients, 26 were lost to follow-up, leaving 62 who completed the 3-month programme. Significant improvements were observed in exercise tolerance (6-min walk test [6MWD]), with mean values increasing from 383.00 ± 71.22 to 441.3 ± 87.3 (P &lt; 0.001). HRQoL, assessed by SGRQ-C, showed an overall improvement, with statistically significant reductions in total scores (42.15 ± 3.52–39.54 ± 3.41, P &lt; 0.001) and in each domain (symptom, impact and activity). Conclusion: The study affirms telerehabilitation’s efficacy in enhancing exercise capacity and improving the quality of life for COPD patients, advocating its integration, particularly in regions with limited access to conventional rehabilitation programmes.

Immune Cell Profile in Young Adults who Regularly Use E-cigarettes and the Role of Nicotine

Background: Cigarette smoking results in altered immune cell function and associated systemic inflammation, as observed in chronic obstructive pulmonary disease (COPD). Electronic (e-) cigarettes are novel, popular tobacco products frequently advertised as a safer alternative to traditional cigarettes; however, the effects of their regular use on immune cell function are currently unknown. Thus, the purpose of this study was to investigate the impact of e-cigarette usage and the role of nicotine on the immune cell profile of young, regular users. Methods: Twenty-five young, apparently healthy, regular users of e-cigarettes (EU, age: 23±3 y.) and twenty-two non-users (NU, age: 23±4 y.) participated in this study. A fasted venous blood sample was obtained from all participants for a complete blood count and nicotine concentrations. EU were randomized to either nicotine or nicotine-free products for fourteen days and completed a second assessment to investigate changes in the immune cell profile based on either increased (+C; n=11) or decreased (-C; n=9) nicotine usage accessed via cotinine levels. For comparison, the same assessments were completed in a group of 13 patients with a diagnosis of COPD (67±9 y., GOLD Stage II-IV). Results: Regular users of e-cigarettes exhibit significantly higher eosinophils (absolute, p=0.008, percentage, p=0.042) and platelets ( p=0.018) when compared to non-users but similar ( p≥0.431) to patients with COPD. White blood cell, neutrophil, monocyte, and lymphocyte counts were similar between the EU and NU. After fourteen days, despite significant changes in nicotine (Δ+C=+2±4 vs. Δ-C=-3±4 ng/mL, p=0.014) and cotinine (Δ+C=+28±27 vs. Δ-C=-141±120 ng/mL, p=0.001) between +C and -C groups, no differences in the immune cell profiles were observed. To note, no association between immune cells and nicotine levels at baseline or follow-up (nicotine: r≤0.352; p≥0.122; cotinine: r≤0.310; p≥0.126). Conclusions: Results of the study suggests that regular users of e-cigarettes present with altered immune cell profile in eosinophils and platelets when compared to non-users. The elevated immune cell markers were comparable to observed values in patients with COPD and have been associated with adverse effects on pulmonary and cardiovascular health. In addition, the elevated immune cell profile was not related to changes in nicotine, inferring that other e-liquid components may have an effect on innate immunity. Future studies are warranted to investigate the long-term effects of e-cigarette use and their components on immune cell profile. Supported in part by a Rapid Response Project NIDA/FDA (PRM). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Diagnosis and Severity Assessment of COPD Using a Novel Fast-Response Capnometer and Interpretable Machine Learning

Introduction Spirometry is the gold standard for COPD diagnosis and severity determination, but is technique-dependent, nonspecific, and requires administration by a trained healthcare professional. There is a need for a fast, reliable, and precise alternative diagnostic test. This study’s aim was to use interpretable machine learning to diagnose COPD and assess severity using 75-second carbon dioxide (CO2) breath records captured with TidalSense’s N-TidalTM capnometer. Method For COPD diagnosis, machine learning algorithms were trained and evaluated on 294 COPD (including GOLD stages 1–4) and 705 non-COPD participants. A logistic regression model was also trained to distinguish GOLD 1 from GOLD 4 COPD with the output probability used as an index of severity. Results The best diagnostic model achieved an AUROC of 0.890, sensitivity of 0.771, specificity of 0.850 and positive predictive value (PPV) of 0.834. Evaluating performance on all test capnograms that were confidently ruled in or out yielded PPV of 0.930 and NPV of 0.890. The severity determination model yielded an AUROC of 0.980, sensitivity of 0.958, specificity of 0.961 and PPV of 0.958 in distinguishing GOLD 1 from GOLD 4. Output probabilities from the severity determination model produced a correlation of 0.71 with percentage predicted FEV1. Conclusion The N-TidalTM device could be used alongside interpretable machine learning as an accurate, point-of-care diagnostic test for COPD, particularly in primary care as a rapid rule-in or rule-out test. N-TidalTM also could be effective in monitoring disease progression, providing a possible alternative to spirometry for disease monitoring.

Severity of Airflow Obstruction Based on FEV1/FVC vs FEV1% of Predicted in the General US Population.

According to GOLD, the ratio of FEV1/FVC is used to confirm airflow obstruction in COPD diagnosis, whereas FEV1% of predicted (FEV1%pred) is used for severity grading. STaging of Airflow obstruction by the FEV1/FVC Ratio (STAR) and its prediction of adverse outcomes has not been evaluated in general populations. To compare the STAR (FEV1/FVC) versus GOLD (FEV1%pred) classification for the severity of airflow limitation in terms of exertional breathlessness and mortality in the general US population. Severity stages according to STAR and GOLD were applied to the multi-ethnic National Health and Nutrition Examination Survey (NHANES) 2007-2012 survey including ages 18-80 years, using post-bronchodilatory FEV1/FVC<0.70 to define airflow obstruction in both staging systems. Prevalence of severity stages STAR 1-4 and GOLD 1-4 was calculated and associations with breathlessness and mortality were analyzed by multinomial logistic regression and Cox regression, respectively. STAR versus GOLD severity staging of airflow obstruction showed similar associations with breathlessness and all-cause mortality, regardless of ethnicity/race. In those with airflow obstruction, the correlation between the two classification systems was 0.461 (p<0.001). STAR reclassified 59% of GOLD stage 2 as having mild airflow obstruction (STAR 1). STAR 1 was more clearly differentiated from the non-obstructive compared to GOLD stage 1 in terms of both breathlessness and mortality. FEV1/FVC and FEV1%pred as measures of severity of airflow limitation show similar prediction of breathlessness and mortality in the adult US population across ethnicity groups. However, stage 1 differed more clearly from non-obstructive based on FEV1/FVC than FEV1%pred. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Improved diagnostic markers for invasive pulmonary aspergillosis in COPD patients.

The prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high mortality. Although early diagnosis can significantly reduce mortality, the efficacy of current diagnostic methods is limited. Consequently, there is a need for novel approaches for early IPA detection. This retrospective study involved 383 hospitalized COPD patients with GOLD stages III and IV. The IPA group (67 patients) and non-IPA group (316 patients) were identified at the First Affiliated Hospital of Guangzhou Medical University between January 2016 and February 2022. We analyzed common serological indicators in our hospital to identify predictive indicators for the early diagnosis of IPA in COPD patients. The sensitivity and specificity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), lactate dehydrogenase (LDH), and ceruloplasmin (CER) for diagnosing IPA in COPD patients were as follows: CRP (91.2%, 57.7%), ESR (77.5%, 73.0%), PCT (60.5%, 71.4%), LDH (50.0%, 88.8%), and CER (60.7%, 74.3%). Combinations of biomarkers, such as CRP-ESR, CRP-LDH, ESR-LDH, ESR-CER, and LDH-CER, showed promising diagnostic potential, with larger area under the curve (AUC) values for IPA diagnosis in COPD patients. However, no statistically significant difference was observed between the diagnostic efficacy of single biomarkers and combined biomarkers. Notably, compared to those in the unassisted ventilation group, the patients in the assisted ventilation group (including noninvasive ventilation and tracheal intubation/incision-assisted ventilation group) exhibited significantly greater PCT and LDH levels, while the CER significantly decreased (p=0.021). There were no significant differences in biomarker levels between the ICU group and the non-ICU group. CRP (p<0.01), ESR (p=0.028), PCT (p<0.01), and CER (p<0.01) were positively correlated with hospitalization duration, whereas LDH was not correlated with hospitalization duration. Our study highlights the diagnostic potential of CRP, ESR, PCT, LDH, and CER for IPA in COPD patients. CRP and LDH can also initially predict the need for assisted ventilation, while CRP can initially estimate the length of hospitalization. This study represents the first report of the potential of CER for diagnosing IPA, suggesting its significance for further research.