asthma-COPD Overlap Research Articles

Assessment of functional diversities in patients with Asthma, COPD, Asthma-COPD overlap, and Cystic Fibrosis (CF).

The objectives of the present study were to evaluate the discriminating power of spirometric and plethysmographic lung function parameters to differenciate the diagnosis of asthma, ACO, COPD, and to define functional characteristics for more precise classification of obstructive lung diseases. From the databases of 4 centers, a total of 756 lung function tests (194 healthy subjects, 175 with asthma, 71 with ACO, 78 with COPD and 238 with CF) were collected, and gradients among combinations of target parameters from spirometry (forced expiratory volume one second: FEV1; FEV1/forced vital capacity: FEV1/FVC; forced expiratory flow between 25-75% FVC: FEF25-75), and plethysmography (effective, resistive airway resistance: sReff; aerodynamic work of breathing at rest: sWOB), separately for in- and expiration (sReffIN, sReffEX, sWOBin, sWOBex) as well as static lung volumes (total lung capacity: TLC; functional residual capacity: FRCpleth; residual volume: RV), the control of breathing (mouth occlusion pressure: P0.1; mean inspiratory flow: VT/TI; the inspiratory to total time ratio: TI/Ttot) and the inspiratory impedance (Zinpleth = P0.1/VT/TI) were explored. Linear discriminant analyses (LDA) were applied to identify discriminant functions and classification rules using recursive partitioning decision trees. LDA showed a high classification accuracy (sensitivity and specificity > 90%) for healthy subjects, COPD and CF. The accuracy dropped for asthma (~70%) and even more for ACO (~60%). The decision tree revealed that P0.1, sRtot, and VT/TI differentiate most between healthy and asthma (68.9%), COPD (82.1%), and CF (60.6%). Moreover, using sWOBex and Zinpleth ACO can be discriminated from asthma and COPD (60%). Thus, the functional complexity of obstructive lung diseases can be understood, if specific spirometric and plethysmographic parameters are used. Moreover, the newly described parameters of airway dynamics and the central control of breathing including Zinpleth may well serve as promising functional marker in the field of precision medicine.

The value of bronchodilator response in FEV1 and FeNO for differentiating between chronic respiratory diseases: an observational study

BackgroundThere is no uniform standard for a strongly positive bronchodilation test (BDT) result. In addition, the role of bronchodilator response in differentiating between asthma, chronic obstructive pulmonary disease (COPD), and asthma–COPD overlap (ACO) in patients with a positive BDT result is unclear. We explored a simplified standard of a strongly positive BDT result and whether bronchodilator response combined with fractional exhaled nitric oxide (FeNO) can differentiate between asthma, COPD, and ACO in patients with a positive BDT result.MethodsThree standards of a strongly positive BDT result, which were, respectively, defined as post-bronchodilator forced expiratory volume in 1-s responses (ΔFEV1) increasing by at least 400 mL + 15% (standard I), 400 mL (standard II), or 15% (standard III), were analyzed in asthma, COPD, and ACO patients with a positive BDT result. Receiver operating characteristic curves were used to determine the optimal values of ΔFEV1 and FeNO. Finally, the accuracy of prediction was verified by a validation study.ResultsThe rates of a strongly positive BDT result and the characteristics between standards I and II were consistent; however, those for standard III was different. ΔFEV1 ≥ 345 mL could predict ACO diagnosis in COPD patients with a positive BDT result (area under the curve [AUC]: 0.881; 95% confidence interval [CI] 0.83–0.94), with a sensitivity and specificity of 90.0% and 91.2%, respectively, in the validation study. When ΔFEV1 was < 315 mL combined with FeNO < 28.5 parts per billion, patients with a positive BDT result were more likely to have pure COPD (AUC: 0.774; 95% CI 0.72–0.83).ConclusionThe simplified standard II can replace standard I. ΔFEV1 and FeNO are helpful in differentiating between asthma, COPD, and ACO in patients with a positive BDT result.

Discordance between Criteria-diagnosed and clinically-diagnosed Asthma COPD Overlap (ACO) among hospitalized patients in an Indian referral hospital.

Background and Objectives: Asthma-COPD-overlap (ACO), as a single entity, has been widely contested over the past few years. Most ACO diagnostic criteria do not agree with each other when applied to respiratory patients. From 2016 to 2020, GINA described a syndromic approach for diagnosing ACO, which was replaced with a broader approach after 2021. We intended to learn if the GINA criteria and the CSMA Screening tool agreed with a clinical diagnosis of ACO. Methods: We performed a retrospective cross-sectional analysis of inpatients with a clinical diagnosis of ACO from 2014 to 2019. We reclassified these patients into Not-ACO and ACO using the GINA syndromic approach 2019 (GSA 2019), Modified GINA syndromic approach 2019 (MGSA 2019), GINA 2021 and the CSMA tool. We used Kappa statistics to compare the performance of various tools. Results: 83 clinically diagnosed ACO patients were included. According to GINA syndromic approach 2019, only 41 (49.39%) patients would be classified as ACO. GINA 2021 picked up 57 (68.67%) patients as ACO. The modified GINA syndromic approach 2019, which we proposed, identified 67 (80.72%) patients as ACO. The CSMA tool identified 63 (75.90%) patients as ACO. The GINA 2019 criteria, when interpreted liberally as described by us, have a better agreement with the CSMA tool with a sensitivity of 87.3% and specificity of 40%, with a 'k' agreement of 29.3%. Conclusion: The standard GINA syndromic approach 2019 Tool is stringent and may sometimes miss the ACO diagnosis. The original GINA syndromic approach table 2019 should be brought back with modifications.

Upregulated microRNA-125b-5p in patients with asthma-COPD overlap mediates oxidative stress and late apoptosis via targeting IL6R/TRIAP1 signaling

BackgroundAmong patients with chronic obstructive pulmonary disease (COPD), some have features of both asthma and COPD—a condition categorized as asthma-COPD overlap (ACO). Our aim was to determine whether asthma- or COPD-related microRNAs (miRNAs) play a role in the pathogenesis of ACO.MethodsA total of 22 healthy subjects and 27 patients with ACO were enrolled. We selected 6 miRNAs that were found to correlate with COPD and asthma. The expression of miRNAs and target genes was analyzed using quantitative reverse-transcriptase polymerase chain reaction. Cell apoptosis and intracellular reactive oxygen species production were evaluated using flow cytometry. In vitro human monocytic THP-1 cells and primary normal human bronchial epithelial (NHBE) cells under stimuli with cigarette smoke extract (CSE) or ovalbumin (OVA) allergen or both were used to verify the clinical findings.ResultsWe identified the upregulation of miR-125b-5p in patients with ACO and in THP-1 cells stimulated with CSE plus OVA allergen. We selected 16 genes related to the miR-125b-5p pathway and found that IL6R and TRIAP1 were both downregulated in patients with ACO and in THP-1 cells stimulated with CSE plus OVA. The percentage of late apoptotic cells increased in the THP-1 cell culture model when stimulated with CSE plus OVA, and the effect was reversed by transfection with miR-125b-5p small interfering RNA (siRNA). The percentage of reactive oxygen species-producing cells increased in the NHBE cell culture model when stimulated with CSE plus OVA, and the effect was reversed by transfection with miR-125b-5p siRNA. In NHBE cells, siRNA transfection reversed the upregulation of STAT3 under CSE+OVA stimulation.ConclusionsOur study revealed that upregulation of miR-125b-5p in patients with ACO mediated late apoptosis in THP-1 cells and oxidative stress in NHBE cells via targeting IL6R and TRIAP1. STAT3 expression was also regulated by miR-125b-5p.

Evaluation of the clinical, demographic and inflammatory characteristics of a Spanish cohort of patients with asthma-COPD overlap syndrome.

Evaluation of the clinical, demographic and inflammatory characteristics of a Spanish cohort of patients with asthma-COPD overlap syndrome.

Differences in the Quantitative HRCT Characteristics of Patients with Asthma, COPD and Asthma-COPD Overlap and Their Relationships with Pulmonary Function.

We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma-COPD overlap (ACO) and explored their relationships with airflow limitation. Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of -860 HU to -950 HU (RVC-860 to-950) and the expiration-to-inspiration ratio of the mean lung density (MLDE/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structure‒function relationships. The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC-860 to -950 levels decreased in the following order: ACO, COPD, and asthma. RVC-860 to -950 independently predicted FEV1% in asthmatic patients; LAA% and MLDE/I in COPD patients; and LAA%, WA% and RVC-860 to -950 in ACO patients. Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.

Common Pathogeneses Underlying Asthma and Chronic Obstructive Pulmonary Disease -Insights from Genetic Studies.

Neither asthma nor chronic obstructive pulmonary disease (COPD) is a single disease consisting of a uniform pathogenesis; rather, they are both syndromes that result from a variety of basic distinct pathogeneses. Many of the basic pathogeneses overlap between the two diseases, and multiple basic pathogeneses are simultaneously involved at varying proportions in individual patients. The specific combination of different basic pathogeneses in each patient determines the phenotype of the patient, and it varies widely from patient to patient. For example, type 2 airway inflammation and neutrophilic airway inflammation may coexist in the same patient, and quite a few patients have clinical characteristics of both asthma and COPD. Even in the same patient, the contribution of each pathogenesis is expected to differ at different life stages (eg, childhood, adolescence, middle age, and older), during different seasons (eg, high seasons for hay fever and rhinovirus infection), and depending on the nature of treatments. This review describes several basic pathogeneses commonly involved in both asthma and COPD, including chronic non-type 2 inflammation, type 2 inflammation, viral infections, and lung development. Understanding of the basic molecular pathogeneses in individual patients, rather than the use of clinical diagnosis, such as asthma, COPD, or even asthma COPD overlap, will enable us to better deal with the diversity seen in disease states, and lead to optimal treatment practices tailored for each patient with less disease burden, such as drug-induced side effects, and improved prognosis. Furthermore, we can expect to focus on these molecular pathways as new drug discovery targets.

Asthma–COPD overlap syndrome among smoker subjects with asthma: A cross-sectional study

This study aimed to assess the prevalence of asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) in asthmatic outpatients with smoking exposure (smokers or ex-smokers with ≥10 pack-year history) and to evaluate quality of life (QoL) and adherence among the study sample. This cross-sectional study was conducted at outpatient respiratory clinics in governmental hospitals in Jordan. Asthmatic outpatients were interviewed to assess their spirometric readings, patients’ adherence, and patients’ QoL [using the Mini Asthma QoL questionnaire (MiniAQLQ)]. The prevalence of ACOS was found to be 33% among asthmatic smoker patients in the outpatient setting (n = 65 out of 200 subjects with asthma-diagnosed patients recruited into the study). For subjects with ACOS, 47.7% of them were older than 60 years old. Smoking history for more than 30 years was prevalent among most subjects with ACOS (67.7%). The MiniAQLQ average score was found to be low (mean ± SD = 3.23 ± 1.01, score out of 7) and similarly for patients’ adherence to their treatment modalities (mean ±SD = 1.76 ± 1.2, score out of 6). A significant positive relationship between adherence to treatment and QoL was found among subjects with ACOS (correlation coefficient = 0.171, p-value = 0.018). In conclusion, a moderate prevalence of ACOS was estimated among asthmatic smoker patients. Low levels of QoL and adherence to treatment were significantly correlated.

A comparison of treatment response to biologics in asthma-COPD overlap and pure asthma: Findings from the PRISM study

BackgroundDespite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. MethodsWe conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and a smoking history of >10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. ResultsAfter six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (−117.50 ± 94.38 vs. −115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (−18.62 ± 24.68 vs. −14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (−3.40 ± 10.60 vs. −14.48 ± 24.01 %, P = 0.065), blood eosinophils (−36.47 ± 517.02 vs. −363.22 ± 1294.59, P = 0.013), and exacerbation frequency (−3.07 ± 4.42 vs. −3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. ConclusionsBiologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.

Effectiveness of rosuvastatin and pulmonary rehabilitation in patients with concurrent course of asthma, chronic obstructive pulmonary disease and diabetes mellitus type 2

The aim of this study was to assess the effectiveness of rosuvastatin and pulmonary rehabilitation in patients with asthma-COPD overlap (ACO) concurrent with type 2 diabetes (T2D).Material and methods. A total of 26 patients with ACO and T2D were examined, with an average age of 61 [55.6; 67.8]. In addition to standard therapy, patients in the main group were prescribed rosuvastatin and a pulmonary rehabilitation program. Treatment efficacy was assessed using questionnaires (CAT, ACQ, SGRQ), dyspnea severity scale (mMRC), BODE index, pulmonary function, bioimpedance analysis, 6-minute walk test, carbohydrate and lipid metabolism status, levels of 8-isoprostane, sCD14, CRP, stable nitric oxide (NO) metabolites - nitrite and nitrate ions, and endothelin-1 in the blood. Results. In the main group, a significant improvement was observed during the treatment course, including a 40% reduction in the BODE index (p&lt;0.05), a 33.4% decrease in dyspnea on the mMRC scale (p&lt;0.05), a 28.5% reduction in CAT, a 40.8% decrease in ACQ, and a 20.6% decrease in SGRQ. Other notable improvements included a 1.3% decrease in BMI, a 13% reduction in body fat percentage, a 23.5% decrease in visceral fat level, a 16% increase in patients' tolerance to physical activity, a 27.5% increase in FEV1 (p&lt;0.05), an 8.1% decrease in fasting blood glucose (p&lt;0.01), a 20% reduction in triglycerides (p&lt;0.05), a 24.9% decrease in LDL cholesterol, and a 27.2% decrease in total cholesterol (p&lt;0.05). Additionally, there was a 23.8% decrease in CRP levels (p&lt;0.05), a two-fold reduction in blood 8-isoprostane levels (p&lt;0.05), a 58% reduction in serum sCD14 levels, a 59.8% increase in stable nitric oxide metabolites (p&lt;0.05), and a 55% decrease in endothelin-1 levels (p&lt;0.05).Conclusions. The use of rosuvastatin and pulmonary rehabilitation significantly improves the quality of life for patients with the concurrent presentation of COPD, asthma, and T2D. It reduces the severity of dyspnea, enhances tolerance to physical activity, improves pulmonary function, lowers visceral fat levels and body fat percentage, enhances lipid profile, and improves endothelial function, all while concurrently reducing oxidative stress and systemic inflammation without worsening carbohydrate metabolism.

Sputum microbiota and inflammatory subtypes in asthma, COPD, and its overlap

BackgroundAirway microbiota in asthma-COPD overlap (ACO) remains unknown. ObjectiveThis study with ACO-enriched population aimed to clarify airway microbiota in ACO and in mixed granulocytic inflammation, often detected in ACO and chronic airway diseases. MethodsThis is an observational cross-sectional study. Patients with asthma with airflow limitation, ACO and COPD were enrolled. Blood tests, pulmonary function, exhaled nitric oxide and sputum tests were conducted. Sputum microbiota was evaluated using the 16S rRNA gene sequencing technique. ResultsA total of 112 patients (13 asthma, 67 ACO, 32 COPD) were examined. There were no significant differences in α-diversity among the three diseases. The relative abundances of phylum Bacteroidetes, class Bacteroidia, and genus Porphyromonas were associated with decreased eosinophilic inflammation, and were significantly lower in ACO than in COPD. In a comparison of sputum inflammatory subtypes, the proportion of Haemophilus was numerically highest in the mixed granulocytic subtype, followed by the neutrophilic subtype. Likewise, the proportion of Haemophilus was the highest in the intermediate-high (2%–8%) sputum eosinophil group and lowest in the severe (8%≤) eosinophil group. Clinically, Haemophilus proportion was associated with sputum symptoms. Finally, the proportion of Streptococcus was associated with higher blood eosinophil counts and severest airflow limitation. ConclusionBacteroidia and Porphyromonas abundances in sputum are associated with the eosinophil-low phenotype, and ACO may be characterised by a decrease in these taxa. A mild elevation of sputum eosinophil does not preclude the presence of Haemophilus, which should be noted in the management of obstructive airway diseases.

Comparison of health-related quality of life measures in asthma-COPD overlap.

The Asthma Quality of Life Questionnaire (AQLQ) and COPD assessment test (CAT) are used to assess the health status of asthma and chronic obstructive pulmonary disease (COPD), respectively. However, whether these questionnaires are appropriate in patients with asthma-COPD overlap (ACO) has not been reported. This study aimed to evaluate the performance of the AQLQ and CAT in subjects with ACO. Subjects were enrolled from two previously described observational studies in Beijing, China. ACO was defined by a consensus definition from a roundtable discussion. All subjects completed the AQLQ, CAT, St George's Respiratory Questionnaire (SGRQ), pulmonary function tests, and the Asthma Control Questionnaire (ACQ)-5. Cross-sectional construct validity was evaluated by correlating the AQLQ and CAT with SGRQ score and other measures of asthma and COPD severity. 147 subjects with ACO were recruited. There were floor effects on non-respiratory components of the CAT, and ceiling effects on emotion domains of the AQLQ. Both questionnaires were significantly correlated with ACQ-5 score but were not correlated with FEV1% predicted or FVC% predicted. The AQLQ and CAT were strongly correlated with SGRQ score (r = -0.657 and r = 0.623, respectively). Multivariable linear regression analysis showed that the AQLQ (standardized β-coefficient = -0.449, p < .001) had a stronger association with SGRQ score compared with CAT (standardized β-coefficient = 0.211, p = .023). The AQLQ and CAT were both valid for assessing the health-related quality of life in subjects with ACO, but the AQLQ performed better than CAT.

Clinical phenotypes of COPD and their impact on quality of life: A cross-sectional study

BackgroundA Chronic Obstructive Pulmonary Disease (COPD) phenotype is a single or group of disease characteristics that describe differences between individuals based on clinically important factors such as symptoms, exacerbations, morbidity, and treatment responses. Many studies estimated the prevalence of various phenotypes, but very few studies looked into their quality of life. We aimed to estimate the prevalence of different COPD phenotypes and their disease-specific Health-Related Quality of Life (HRQoL). Materials and methodsThe prospective study, with a sample size of 136, was conducted between May 2021 and December 2022 in a tertiary teaching institute. Based on their clinical features, COPD patients were classified into 4 different clinical phenotypes, and their disease-specific quality of life was assessed using St. George Respiratory Questionnaire-COPD(SGRQ-c) and COPD Assessment Test (CAT) questionnaires. ResultsAmong 136 COPD patients, the frequency of Non-Exacerbator (NE), Exacerbator Emphysema (EEM), Exacerbator Chronic Bronchitis (ECB), and Asthma COPD overlap (ACO) phenotypes was 79(58.1 %), 16(11.8 %), 31(22.8 %), and 10(7.4 %) respectively. Based on the SGRQ-c score, the ECB and EEM phenotypes had a significantly poorer Quality of life (QoL) when compared with NE(P<0.0001), ACO(P=0.011), phenotypes. Similarly, ECB and EEM phenotypes had significantly poorer QoL when compared to NE(P<0.0001), and ACO(P=0.015), based on the CAT score. ECB and EEM patients also had the worst scores in all individual CAT items and SGRQ-c components. ConclusionNE was the most common followed by ECB phenotype. ECB and EEM phenotypes recorded the poorest quality of life without any significant differences among them. Further research is needed in the future to determine whether phenotype-specific therapies can produce better clinical outcomes.

Evaluation of the prevalence of asthma and chronic obstructive pulmonary disease among opium users, and cigarette smokers and comparison with normal population in Kharameh: a cross-sectional study.

Recent studies have suggested that opium use may increase mortality from pulmonary diseases. However, there are limited comprehensive studies regarding the prevalence of Asthma and Chronic Obstructive Pulmonary Disease (COPD) among tobacco and opium users has been published. We aimed to determine the prevalence of respiratory disease among tobacco and opium users. This cross-sectional study of tobacco and opium users and matched controls was conducted in the Kharameh Cohort, Fars, Iran. The prevalence of COPD and asthma, along with the participants demographical and spirometry data were examined. The average age of participants was 57 ± 8 years. Never smokers had a significant higher BMI (26.6 vs. 24.8), FEV1 (91% vs. 82%) and FVC (96% vs. 88%) values compared to participants with a positive smoking status. There was a statistical difference in the prevalence of COPD, asthma, and asthma COPD overlap (ACO) based on the participants smoking status, with the highest prevalence among opium and cigarette smokers, followed by opium users alone. Based on multivariate analysis, higher age, lower BMI, lower education than under diploma, cigarette smoking and opium use were significantly correlated with higher COPD prevalence; while lower age, cigarette smoking and opium use were significantly correlated with higher asthma prevalence. Illiterate participants had a significantly higher prevalence of COPD (23.6%), asthma (22%), and ACO (7.9%) among the educational groups. Regarding the prevalence of asthma, the higher socio-economic group had the lowest prevalence. Opium and tobacco users had a significantly higher prevalence of respiratory diseases, along with lower lung function tests based on spirometry evaluation.

Modulating asthma-COPD overlap responses with IL-17 inhibition.

IL-17 is a modulator of the inflammatory response and is implicated in lung remodeling in both asthma and chronic obstructive pulmonary disease (COPD). Well as and probably in patients with asthma-COPD overlap (ACO). In this study, we evaluated the response of the airways and alveolar septa to anti-IL-17 treatment in an ACO model. Fifty-six male BALB/c mice were sensitized with ovalbumin (OVA group), received porcine pancreatic elastase (PPE group), or both (ACO group). Mice were then treated with either anti-IL-17 monoclonal antibody or saline. We evaluated hyperresponsiveness, bronchoalveolar lavage fluid (BALF) cell counts, and mean alveolar diameter. We quantified inflammatory, response, extracellular matrix remodeling, oxidative stress markers, and signaling pathway markers. Anti-IL-17 treatment in the ACO anti-IL-17 group reduced the maximum response of respiratory system Rrs, Ers, Raw, Gtis, this when compared to the ACO group (p<0.05). There was a reduction in the total number of inflammatory cells, neutrophils, and macrophages in the BALF in the ACO anti-IL-17 group compared to the ACO group (p<0.05). There was attenuated dendritic cells, CD4+, CD8+, FOXP3, IL-1β, IL-2, IL-6, IL-13, IL-17, IL-33 in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p<0.05). We observed a reduction of MMP-9, MMP-12, TIMP-1, TGF-β, collagen type I in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p < 0.05). We also observed a reduction of iNOS and 8-iso-PGF2α in the airways and in the alveolar septum was reduced in the ACO anti-IL-17group compared to the ACO group (p < 0.05). Regarding the signaling pathways, NF-kB, ROCK-1, and ROCK-2 in the airway and alveolar septum were attenuated in the ACO anti-IL-17 group when compared to the ACO group (p<0.05). Our results suggest that inhibiting IL-17 modulates cell-associated cytokine production in lung tissue, extracellular matrix remodeling, and oxidative stress in ACO through the modulation of NF-kB and FOXP3.

Lactobacillus rhamnosus Modulates Lung Inflammation and Mitigates Gut Dysbiosis in a Murine Model of Asthma-COPD Overlap Syndrome.

The asthma-COPD overlap syndrome (ACOS) presents lung inflammation similar to both asthma and chronic obstructive pulmonary disease (COPD). Due to the immune response between the lung and gut, it is possible that ACOS individuals present gut dysbiosis. Due to therapeutic limitations in ACOS, Lactobacillus rhamnosus (Lr) have received attention once Lr has been effective in asthma and COPD. However, there is no data about the Lr effect on both lung inflammation and gut dysbiosis in ACOS. Thus, our study investigated the Lr effect on lung inflammation, bronchoconstriction, airway remodeling, and gut dysbiosis in the murine ACOS model. Treated mice with Lr were exposed to HDM and cigarette smoke to induce ACOS. Sixty days after ACOS induction, mice were euthanized. Lung inflammation was evaluated in leukocytes in bronchoalveolar lavage fluid (BALF), airway remodeling, cytokine secretion, and transcription factor expression in the lung. The gut microbiota was assayed by 16S mRNA sequencing from a fecal sample. Leukocyte population, bronchial hyperreactivity, pro-inflammatory cytokines, and airway remodeling were attenuated in Lr-treated ACOS mice. Likewise, IL-4, IL-5, and IL-13, STAT6 and GATA3, as well as IL-17, IL-21, IL-22, STAT3, and RORɣt were reduced after Lr. In addition, IL-2, IL-12, IFN-γ, STAT1, and T-bet as well as IL-10, TGF-β, STAT5, and Foxp3 were restored after the Lr. Firmicutes was reduced, while Deferribacteres was increased after Lr. Likewise, Lr decreased Staphylococcus and increased Mucispirillum in ACOS mice. Lr improves fecal bacterial β-diversity. Our findings show for the first time the Lr effect on lung inflammation and gut dysbiosis in murine ACOS.

Overcoming the Digital Divide for Older Patients With Respiratory Disease: Focus Group Study.

The need for and adoption of eHealth programs are growing worldwide. However, access can be limited among patients with low socioeconomic backgrounds, often resulting in a so-called "digital divide" due to a mismatch between eHealth and target populations that can gain benefit. This digital divide can result in unsuccessful eHealth implementations, which is of critical importance to health care. This study evaluated the opinions of elderly patients with asthma and chronic obstructive pulmonary disease (COPD) about an existing pharmacy-based personalized patient web portal that provides medication overview and information on associated diagnoses. The aim was to obtain insights on the common barriers of elderly people when using health-related websites, which can help to improve accessibility. This was a cross-sectional qualitative study of a patient panel of the Groningen Research Institute for Asthma and COPD in primary care. Participants were required to be older than 55 years, be Dutch speaking, have no prior experience with the study website, and be diagnosed with a chronic respiratory illness. Two focus groups were created, and they completed a 45-minute session for testing the website and a 120-minute session for semistructured interviews. The focus group sessions were recorded, transcribed verbatim, and analyzed by content analysis. We enrolled 11 patients (9 women) with a mean age of 66 (SD 9) years. Of these, 5 had asthma, 3 had COPD, 2 had asthma-COPD overlap syndrome, and 1 had bronchiectasis. Participants were generally positive about the website, especially the areas providing disease-related information and the medication overview. They appreciated that the website would enable them to share this information with other health care providers. However, some difficulties were reported with navigation, such as opening a new tab, and others reported that the layout of the website was difficult either because of visual impairments or problems with navigation. It was also felt that monitoring would only be relevant if it is also checked by health care professionals as part of a treatment plan. Participants mentioned few privacy or safety concerns. It is feasible to develop websites for elderly patients; however, developers must take the specific needs and limitations of elderly people into account (eg, navigation problems, poor vision, or poor hand-eye coordination). The provision of information appears to be the most important aspect of the website, and as such, we should endeavor to ensure that the layout and navigation remain basic and accessible. Patients are only motivated to use self-management applications if they are an integrated part of their treatment. The usability of the website can be improved by including older people during development and by implementing design features that can improve accessibility in this group.

Biomarkers in exhaled breath condensate as fingerprints of asthma, chronic obstructive pulmonary disease and asthma-chronic obstructive pulmonary disease overlap: a critical review.

Asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap are the third leading cause of mortality around the world. They share some common features, which can lead to misdiagnosis. To properly manage these conditions, reliable markers for early and accurate diagnosis are needed. Over the past 20years, many molecules have been investigated in the exhaled breath condensate to better understand inflammation pathways and mechanisms related to these disorders. Recently, more advanced techniques, such as sensitive metabolomic and proteomic profiling, have been used to obtain a more comprehensive understanding. This article reviews the use of targeted and untargeted metabolomic methodology to study asthma, COPD and asthma-COPD overlap.

Association of cigarette smoking with increased use of heated tobacco products in middle-aged and older adults with self-reported chronic obstructive pulmonary disease, asthma, and asthma-COPD overlap in Japan, 2022: the JASTIS study

BackgroundSmoking cessation is the most important intervention in chronic obstructive pulmonary disease (COPD), asthma, and asthma-COPD overlap (ACO); however, high rates of current cigarette smoking are observed in adults with these respiratory diseases. Meanwhile, rapidly increasing use of heated tobacco products (HTPs) is observed in Japan; however, the status of HTPs use has not been fully understood in adults with COPD, asthma, and ACO. This study aimed to reveal the association between COPD, asthma, and ACO and HTPs use in adults.MethodsData on Japanese individuals ≥ 40 years old obtained from the Japan Society and New Tobacco Internet Survey were analyzed. The prevalence of HTPs use in adults with COPD, asthma, and ACO, among individuals categorized into three groups according to cigarette smoking (never, former, and current), was calculated and the relationship between each disease and HTPs use were evaluated. The clinical diagnosis of these diseases was based on the self-reported diagnosis, as obtained from questionnaires.ResultsA total of 19,308 individuals were included. The proportions of never, past, and current cigarettes smokers were 10,900 (56.5%), 4,903 (25.4%), and 3,505 (18.2%), respectively, and that of HTPs use was 1,813 (9.4%). In current cigarettes smokers, the adjusted odds ratios (ORs) of HTPs use was 2.88 (95% CI [confidence interval], 1.86–4.47), 1.23 (95% CI, 0.99–1.52), and 5.81 (95% CI, 3.12–10.82) in adults with COPD, asthma, and ACO compared to those without these respiratory diseases, respectively. Meanwhile, in past cigarettes smokers, the adjusted ORs of HTPs use was 0.51 (95% CI, 0.24–1.08), 0.69 (95% CI, 0.53–0.88), and 0.25 (95% CI, 0.06–1.07) in adults with COPD, asthma, and ACO, respectively.ConclusionsHTPs use is more prevalent among current cigarettes smokers with COPD, asthma, and ACO compared to those without these respiratory diseases. Complete cessation of smoking both cigarettes and HTPs is the only way to achieve complete smoking cessation, therefore, adults with COPD, asthma, and ACO need to make greater efforts to quit smoking.

Investigating the Effects of a New Peptide, Derived from the Enterolobium contortisiliquum Proteinase Inhibitor (EcTI), on Inflammation, Remodeling, and Oxidative Stress in an Experimental Mouse Model of Asthma-Chronic Obstructive Pulmonary Disease Overlap (ACO).

The synthesized peptide derived from Enterolobium contortisiliquum (pep3-EcTI) has been associated with potent anti-inflammatory and antioxidant effects, and it may be a potential new treatment for asthma-COPD overlap-ACO). Purpose: To investigate the primary sequence effects of pep3-EcTI in an experimental ACO. BALB/c mice were divided into eight groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep3-EcTI (treated with inhibitor), ACO-DX (treated with dexamethasone), ACO-DX-pep3-EcTI (treated with dexamethasone and inhibitor), and SAL-pep3-EcTI (saline group treated with inhibitor). We evaluated the hyperresponsiveness to methacholine, exhaled nitric oxide, bronchoalveolar lavage fluid (BALF), mean linear intercept (Lm), inflammatory markers, tumor necrosis factor (TNF-α), interferon (IFN)), matrix metalloproteinases (MMPs), growth factor (TGF-β), collagen fibers, the oxidative stress marker inducible nitric oxide synthase (iNOS), transcription factors, and the signaling pathway NF-κB in the airways (AW) and alveolar septa (AS). Statistical analysis was conducted using one-way ANOVA and t-tests, significant when p < 0.05. ACO caused alterations in the airways and alveolar septa. Compared with SAL, ACO-pep3-EcTI reversed the changes in the percentage of resistance of the respiratory system (%Rrs), the elastance of the respiratory system (%Ers), tissue resistance (%Gtis), tissue elastance (%Htis), airway resistance (%Raw), Lm, exhaled nitric oxide (ENO), lymphocytes, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, transforming growth factor (TGF)-β, collagen fibers, and iNOS. ACO-DX reversed the changes in %Rrs, %Ers, %Gtis, %Htis, %Raw, total cells, eosinophils, neutrophils, lymphocytes, macrophages, IL-1β, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, TGF-β, collagen fibers, and iNOS. ACO-DX-pep3-EcTI reversed the changes, as was also observed for the pep3-EcTI and the ACO-DX-pep3-EcTI. Significance: The pep3-EcTI was revealed to be a promising strategy for the treatment of ACO, asthma, and COPD.