Chronic Obstructive Lung Disease Research Articles

Diagnosing and Treating Chronic Obstructive Pulmonary Disease in 2024 – What Is New?

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) lays down guidelines and strategies for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (COPD). Recently, the GOLD 2024 guidelines have been released. This brief report discusses the updates along with underlying evidence.

Use of inhaled solution of hypertonic saline combined with high-molecular-weight hyaluronic acid in patients with lower respiratory tract diseases

Resolution of the Council of ExpertsNovember 17, 2023Respiratory diseases (acute and chronic bronchitis, chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis (CF), bronchial asthma, etc.) are often accompanied by impaired mucus clearance. In this regard, mucoactive drugs are most commonly used for the treatment. Hypertonic saline plus high-molecular-weight hyaluronic acid is one of the affordable and effective agents that can help with thinning and removal of bronchial secretions. The effect of 3%, 6%, 7% hypertonic saline on the respiratory system is multifaceted: it stimulates the osmotic fluid flow, breaks bonds linking polymers in the sputum, reduces swelling in the mucous membranes, stimulates ciliary beat frequency, and reduces the neutrophilic inflammation severity. The molecular size of HA plays an important role in the effectiveness of inhalation therapy with hypertonic saline combined with hyaluronic acid (HA). External administration of high-molecular-weight hyaluronic acid inhibits neutrophil elastase and metalloproteinase, potentiates hydration of bronchial secretions and has anti-inflammatory properties. In addition to clinical studies, real-life clinical practice in patients with cystic fibrosis, bronchiectasis and acute bronchitis also demonstrated the effectiveness of hypertonic saline combined with high-molecular-weight hyaluronic acid. The rationale for the use of hypertonic saline was reflected in the international GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines in 2023. Therefore, due to high interest in the hypertonic saline combined with high-molecular-weight hyaluronic acid, it is important to expand the evidence base: to initiate a Russian multicenter study evaluating the effectiveness and safety of this combination in patients with chronic bronchitis and COPD in the Russian Federation. It will allow us to recommend hypertonic saline combined with high-molecular-weight hyaluronic acid to be included in the Russian clinical guidelines on treatment of chronic bronchitis and COPD as a mucoactive drug.

Comparison of Factors Affecting the Immune Response to Hepatitis B Vaccination in Patients with Stage 5 Chronic Kidney Disease-haemodialysis and Predialysis

Aim To evaluate the factors that affect the immune response to Hepatitis B vaccination in the Stage 5 chronic kidney disease population (Haemodialysis and Predialysis). Methods Eligible Stage 5 chronic kidney disease patients on haemodialysis (Cohort A: N= 39) and Predialysis (Cohort B: N=56) in an outer metropolitan renal service in Western Australia with no prior Hepatitis B infection or vaccination between Jan 2015 to Dec 2021 were involved in this retrospective cohort study. Serological response to Hepatitis B vaccination (H-B-VAX II 40 mcg intramuscularly at 0, 1 and 6 months) was evaluated six-eight weeks post-vaccination. Factors such as age, gender, diabetes mellites, cardiovascular disease, hypertension, chronic obstructive airway disease, serum albumin, and erythropoietin stimulating agent dependence were studied for their influence on immune responses in these cohorts. Results There were 95 eligible respondents in the study. Cohort B (Predialysis) showed a significantly higher response than Cohort A (Haemodialysis) (66.1% vs 53.8%) (p=0.003). Different factors affecting the vaccine response were identified in the two cohorts. Serum albumin <35g/L was associated with negative response in 61.1% (p =0.0023)Cohort A HD patients. In the Predialysis Cohort B, 84.2%(p=0.026) were male gender, 63.2%(p=0.028) with the presence of cardiovascular disease, and 57.9%(p=0.001) who were Erythropoietin dependent showed a negative response to the vaccine. Conclusion This study showed that the Hepatitis B vaccine response was lower in HD patients than in Predialysis patients with stage 5 chronic kidney disease. Clinical factors of serum albumin, cardiovascular disease, and patient factors of gender and erythropoietin dependence were identified as factors that affected vaccine response in these two cohorts. We postulate these factors to be considered in the hepatitis B vaccination management to enhance immunological response strategies and extend to earlier stages of chronic kidney failure.

Exacerbation-like events in the 12 months prior to identification of chronic respiratory conditions in a primary care population

Initial chronic obstructive lung disease (COPD) pharmacotherapy is based on symptom burden and exacerbation history. Inclusion of inhaled cortico-steroids (ICS) is recommended only for those with a history of exacerbations. This brief report highlights that among individuals with previously unrecognized COPD about 1 in 5 have one or more exacerbation-like events and about 1 in 10 have two or more events in the prior 12 months whether or not they self-report concomitant asthma. Closer attention to prior exacerbation-like event history might lead to more guideline concordant care.In addition, there are two other groups that have impaired but non-obstructive spirometry, some with significant respiratory symptom burden who have frequencies of exacerbation-like events similar to those meeting COPD spirometry criteria. To date we have little guidance for treatment of these individuals.

Gait analysis and geriatric syndromes: An association among elderly patients attending a teaching hospital of Delhi

ABSTRACT Background: Gait abnormalities are prevalent, affecting a substantial portion of the elderly population, and leading to mobility limitations, reduced quality of life, falls, hospitalizations, and premature death. Objectives: The study aims to assess gait patterns among individuals aged 75 years and above attending the geriatric OPD of a tertiary care hospital in New Delhi and evaluate their association with various geriatric syndromes. Materials and Methods: This cross-sectional study, conducted at a tertiary care hospital in Delhi, from May 2019 to November 2021, involved 100 participants aged 75 and above. It encompassed a thorough assessment protocol covering demographics, health history, clinical and functional evaluations, depression, cognition, balance, frailty, urinary incontinence, polypharmacy, nutrition, comorbidities, and gait analysis. Results: In this study of elderly individuals, the mean age was 78.56 years, and the mean BMI was 23.11. The participants had an average of 1.74 comorbidities, with hypertension being the most prevalent (62%), followed by diabetes (25%), chronic obstructive airway disease (COAD) (11%), and coronary artery disease (15%). Geriatric assessments revealed varying proportions of frailty (34%), polypharmacy (40%), and urinary incontinence (9%). The mean scores for activities of daily living, instrumental activities of daily living, nutritional status, cognitive function, Timed Up and Go Test, and depression scale were also reported. Various gait parameters demonstrated significant correlations with these geriatric factors, including frailty, comorbidities, BMI, and mobility scores. Conclusion: The study identified significant associations between gait patterns and various geriatric syndromes, emphasizing the importance of gait analysis in assessing the health and mobility of elderly individuals.

Phenotyping chronic respiratory diseases with airways obstruction.

<sec id="st1"><title>BACKGROUND</title>Given the high prevalence of asthma-chronic obstructive pulmonary disease overlap (ACO) in Vietnam, there is an urgent need to establish a simplified strategy for categorising patients as either having asthma or chronic obstructive pulmonary disease (COPD). This classification would streamline the application of treatment recommendations outlined by the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).</sec><sec id="st2"><title>METHODS</title>Patients with obstructive lung function were classified as having COPD, asthma, or ACO based on GINA/GOLD guidelines. We hypothesised that ACO-like asthma (ACO-A) would present with positive skin prick tests (SPTs) or early onset of symptoms without a history of tuberculosis (TB), while those with ACO-like COPD (ACO-B) would exhibit negative SPTs and late onset of symptoms and/or a history of TB.</sec><sec id="st3"><title>RESULTS</title>Among 235 patients, the prevalence of asthma, ACO-A, ACO-B, and COPD was respectively 21%, 22%, 17%, and 40%. Allergic history, rhinitis, and childhood asthma were associated with ACO-A, while high cumulative smoking was correlated with ACO-B. Socio-economic and demographic parameters, medical history, clinical features, smoking habits, lung function, and para-clinical investigations significantly differed between "all asthma" (i.e., individuals with asthma combined with ACO-A) and "all COPD" (i.e., individuals with COPD combined with ACO-B).</sec><sec id="st4"><title>CONCLUSION</title>Based on SPTs, history of TB, and onset age, ACO patients may be defined as people with asthma or COPD.</sec>.

Home non-invasive ventilation: An observational study of aetiology, chronic respiratory failure of multiple aetiologies, survival and treatment adherence

Home non-invasive ventilation (NIV) is used to treat patients with chronic respiratory failure (CRF). However, knowledge on the prevalence and impact of multimorbid aetiology of CRF, patterns of NIV use, and survival of these patients is limited. Our aim was to analyse the multiple aetiologies of CRF, patterns of NIV use and the outcome of those patients.We conducted a retrospective analysis of 1,281 patients treated with home-NIV between 2004 and 2014 in Turku University Hospital, Finland. The patients were divided into nine disease categories: obstructive airways disease (16 %); obesity hypoventilation syndrome (11 %); neuromuscular disease (10 %); chest wall diseases (4 %); sleep apnoea (26 %); interstitial lung diseases (3 %); malignancy (2 %); other (3 %) and acute (8 %), which refers to the patients who did not fulfil criteria of CRF. In addition, multiple aetiologies of CRF were found in 17 %. Mean adherence to home-NIV was 6.0 ± 4.4 h/d and median treatment duration 410 (120–1021) days. Adherence, treatment duration or survival did not significantly differ between patients with either single or multiple causative diseases leading to CRF. Median survival was 4.5 years (95 % CI 3.6 to 5.4). The main reasons for discontinuing NIV were death (56 %) and lack of motivation (19 %).We conclude that home-NIV is used in a variety of diseases. CRF of multiple aetiologies is prevalent and not limited to chronic obstructive lung disease and obstructive sleep apnoea overlap syndrome. However, the adherence to home-NIV or survival did not differ between patients with a single or multiple diseases causing CRF, but the survival of the home-NIV patients differed according to the underlying aetiology of CRF.

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).

HF Etiology and cardiac contractility modulation therapy

ObjectivesOur study aimed to assess the safety and efficacy of cardiac contractility modulation (CCM) therapy in patients with heart failure with reduced ejection fraction (HFrEF) depending on HF etiology.MethodsWe enrolled 166 patients with optimal medical therapy-resistant HFrEF (median age 59 years, 83.7% males, median NYHA class − 2, median left ventricular ejection fraction (LVEF) − 29.0%) who underwent CCM therapy device implantation from 2013 to 2019 in four medical centers in Russia. The HF etiology was determined based on invasive coronary angiography or cardiac MRI data. Transthoracic echocardiography (TTE), 6-minute walking test (6MWT), and NTproBNP-tests were performed at a baseline and 12 months after the implantation.ResultsThe ischemic etiology of HF was revealed in 100 patients (61.5%) (ICM group); the non-ischemic group (NICM) evolved 66 patients (38.5%). Patients in the ICM group were significantly older (61[57–69] vs. 55 [42.8–61], p < 0.001), more frequently had hypertension (79% vs. 42.4%, p < 0.001) and chronic kidney disease (43% vs. 22.7%, p = 0.012). Patients in the NICM group had significantly more often atrial fibrillation (AF) (58% vs. 74%, p = 0.048), larger end-diastolic volume (EDV) (249 [208–309] vs. 220 [192–271], p = 0.019) and end-systolic volume (ESV) (183 [147–230] vs. 154 [128–199], p = 0.003). There were no significant differences in mortality between ICM and NICM groups (14.4 vs. 10.8%, p = 0.51). In 12 months, there was a significant increase in LVEF in the NICM group (+ 2.0 [2–6] vs. +7.7 [2–12], p < 0.001), while the improvement in the 6MWT (+ 75 [22–108] vs. +80 [10–160], p = 0.851) and NYHA class did not reach the level of significance. The subanalysis between patients with improved NYHA class and those without improvement revealed that patients without improvement more frequently had AF (56% vs. 89%; p < 0.01), chronic obstructive lung disease (18% vs. 35% p = 0.047), higher blood pressure (110 [105–120] vs. 120[110–129]; p = 0.032).ConclusionIn this multicenter retrospective study, patients with non-ischemic HFrEF showed a significantly higher improvement in LVEF and LV reverse remodeling following CCM therapy device implantation. There was no significant association between HF etiology and survival in drug-resistant HFrEF patients following CCM therapy.

Clinical guideline highlights for the hospitalist: GOLD COPD update 2024.

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2024 Report) RELEASE DATE: December 4, 2023 PRIOR VERSIONS: Initial report was released in 2001 with major revisions in 2006, 2011, 2017, and 2023. This 2024 release is an update to the 2023 major revision DEVELOPER: Global Initiative for Chronic Obstructive Lung Disease (GOLD) FUNDING SOURCE: GOLD TARGET POPULATION: Adults with a diagnosis of or at risk for COPD.

Effects of combustible cigarettes and heated tobacco products on immune cell-driven inflammation in chronic obstructive respiratory diseases.

Since long-term effects of heated tobacco products (HTP) on the progression of chronic obstructive pulmonary disease (COPD) are unknown, we used COPD mice model to compare immune cell-dependent pathological changes in the lungs of animals which were exposed to HTP or combustible cigarettes (CCs). We also performed intracellular staining and flow cytometry analysis of immune cells which were present in the blood of CCs and HTP users who suffered from immune cell-driven chronic obstructive respiratory diseases. CCs enhanced NLRP3 inflammasome-dependent production of inflammatory cytokines in lung-infiltrated neutrophils and macrophages and increased influx of cytotoxic Th1, Th2, and Th17 lymphocytes in the lungs of COPD mice. Similarly, CCs promoted generation of inflammatory phenotype in circulating leukocytes of COPD patients. Opposite to CCs, HTP favored expansion of immunosuppressive, IL-10-producing, FoxP3-expressing T, NK, and NKT cells in inflamed lungs of COPD mice. Compared with CCs, HTP had weaker capacity to promote synthesis of inflammatory cytokines in lung-infiltrated immune cells. Significantly lower number of inflammatory neutrophils, monocytes, Th1, Th2, and Th17 lymphocytes were observed in the blood of patients who consumed HTP than in the blood of CCs users, indicating different effects of CCs and HTP on immune cells' phenotype and function.

An update on COPD prevention, diagnosis, and management: The 2024 GOLD Report.

Chronic obstructive pulmonary disease (COPD) is one of the top three causes of death throughout the world. Because of the preventable and treatable nature of the disease along with its prevalence, COPD represents a major public health challenge. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Report provides a review of the most current evidence for prevention of COPD as well as the assessment, diagnosis, and treatment of people with the disease. The purpose of this article is to provide a summary of the 2024 revised GOLD Report and current best practices in accordance with the evidence.

Evaluating Quality of Care for Patients with Asthma in the Readmission Penalty Era.

Rationale: Asthma poses a significant burden for U.S. patients and health systems, yet inpatient care quality is understudied. National chronic obstructive lung disease (COPD) readmission policies may affect inpatient asthma care through hospital responses to these policies because of imprecise diagnosis and identification of patients with COPD and asthma. Objectives: Evaluate inpatient care quality for patients hospitalized with asthma and potential collateral effects of the Medicare COPD Hospital Readmissions Reduction Program (HRRP). Methods: This was a retrospective cohort study of patients aged 18-54 years hospitalized for asthma across 924 U.S. hospitals (Premier Healthcare Database). Results: Care quality for patients with asthma was evaluated before HRRP implementation (n = 20,820; January 2010-September 2014) and after HRRP implementation (n = 26,885; October 2014-December 2018) using adherence to inpatient care guidelines (recommended, nonrecommended, and "ideal care" [all recommended with no nonrecommended care]). Between 2010 and 2018, at least 80% of patients received recommended care annually. Recommended care decreased similarly (rate of 0.02%/mo) after versus before HRRP (P = 0.8). Nonrecommended care decreased more rapidly after HRRP (rate of 0.29%/mo) versus before HRRP (rate of 0.17%/mo; P < 0.001), with changes driven largely by decreased antibiotic prescribing. Ideal care increased more rapidly after HRRP (rate of 0.25%/mo) versus before HRRP (rate of 0.17%/mo; P = 0.02), with changes driven largely by nonrecommended care improvements. Conclusions: Post-HRRP trends suggest asthma care improved with increased rates of guideline concordance in nonrecommended and ideal care. Although federal policies (e.g., HRRP) may have had positive collateral effects, such as with asthma care, parallel care efforts, including antibiotic stewardship, likely contributed to these improvements.

The prevalence and mortality risks of PRISm and COPD in the United States from NHANES 2007–2012

BackgroundWe estimated the prevalence and mortality risks of preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) in the US adult population.MethodsWe linked three waves of pre-bronchodilator spirometry data from the US National Health and Nutritional Examination Survey (2007–2012) with the National Death Index. The analytic sample included adults ages 20 to 79 without missing data on age, sex, height, BMI, race/ethnicity, and smoking status. We defined COPD (GOLD 1, 2, and 3–4) and PRISm using FEV1/FVC cut points by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the prevalence of GOLD stages and PRISm by covariates across the three waves. We estimated adjusted all-cause and cause-specific mortality risks by COPD stage and PRISm using all three waves combined.ResultsPrevalence of COPD and PRISm from 2007–2012 ranged from 13.1%-14.3% and 9.6%-10.2%, respectively. We found significant differences in prevalence by sex, age, smoking status, and race/ethnicity. Males had higher rates of COPD regardless of stage, while females had higher rates of PRISm. COPD prevalence increased with age, but not PRISm, which was highest among middle-aged individuals. Compared to current and never smokers, former smokers showed lower rates of PRISm but higher rates of GOLD 1. COPD prevalence was highest among non-Hispanic White individuals, and PRISm was notably higher among non-Hispanic Black individuals (range 31.4%-37.4%). We found associations between PRISm and all-cause mortality (hazard ratio [HR]: 2.3 95% CI: 1.9—2.9) and various cause-specific deaths (HR ranges: 2.0–5.3). We also found associations between GOLD 2 (HR: 2.1, 95% CI: 1.7–2.6) or higher (HR: 4.2, 95% CI: 2.7–6.5) and all-cause mortality. Cause-specific mortality risk varied within COPD stages but typically increased with higher GOLD stage.ConclusionsThe prevalence of COPD and PRISm remained stable from 2007–2012. Greater attention should be paid to the potential impacts of PRISm due to its higher prevalence in minority groups and its associations with mortality across various causes including cancer.

Maintenance Pulmonary Rehabilitation: An Update and Future Directions.

The Global Initiative for Chronic Obstructive Lung Disease guidelines recommend pulmonary rehabilitation (PR) for individuals with COPD to improve exercise capacity and health-related quality of life (HRQOL) and reduce symptoms of dyspnea. For cost-effectiveness in COPD care, PR is second only to smoking cessation. However, PR programs typically last 9-12 weeks. The benefits of PR in terms of exercise capacity and HRQOL often decrease toward pre-PR levels as early as 3-6 months after completing PR if patients do not continue to engage in exercise. This review will (1) briefly summarize the efficacy data that informed the 2023 American Thoracic Society (ATS) clinical practice guidelines for maintenance PR, (2) discuss exercise components of maintenance PR studied since 2020 when the last papers were included in the ATS guidelines, (3) explore future directions for delivery of maintenance PR using technology-mediated models, and (4) examine the need for behavior change techniques informed by theoretical models that underpin long-term behavior change. This review will focus on persons with COPD who have completed an out-patient core initial PR program as most of the data on maintenance PR have been published in this patient population. Core PR typically implies a facility-based initial intensive structured program. All patients who complete a core initial PR program should be counseled by PR staff at the discharge visit to engage in ongoing exercise. This usual care is equally as important as referral to a formal PR maintenance program. It is critical to emphasize that usual care after core initial PR means all patients should be supported to participate in regular ongoing exercise, regardless of whether supervised maintenance PR is available. Currently, the optimal frequency, exercise and/or physical activity content, and delivery mode for maintenance PR in persons with COPD and other chronic respiratory diseases remain unknown. Patient safety and degree of in-person supervision required due to the severity of the underlying lung disease need to be considered. Future research of maintenance PR should be underpinned by behavior change techniques. Finally, in the setting of finite resources, balancing the competing priorities of core initial programs with those of maintenance PR programs needs to be achieved.

Blood eosinophils levels in a Colombian cohort of biomass-and tobacco-related COPD patients.

Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death among adults. In 2019, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy incorporated blood eosinophils as a biomarker to identify patients at increased risk of exacerbations which, with the history of exacerbations during the previous year, allows identification of patients who would benefit from anti-inflammatory treatment to reduce the risk of future exacerbations. The aim of this study was to describe demographic and clinical characteristics, eosinophil counts, and exacerbations in a cohort of COPD patients stratified by clinical phenotypes (non-exacerbator, frequent exacerbator, asthma-COPD overlap) in a Colombian cohort at 2600 meters above sea level. A descriptive analysis of a historical cohort of patients with a confirmed diagnosis of moderate to severe COPD (FEV1/FVC < 0.7 and at least one risk factor for COPD) from two specialized centers with comprehensive disease management programs was performed from January 2015 to March 2019. Data were extracted from medical records 1 year before and after the index date. 200 patients were included (GOLD B: 156, GOLD E: 44; 2023 GOLD classification); mean age was 77.9 (SD 7.9) years; 48% were women, and 52% had biomass exposure as a COPD risk factor. The mean FEV1/FVC was 53.4% (SD 9.8), with an FEV1 of 52.7% (20.7). No differences were observed between clinical phenotypes in terms of airflow limitation. The geometric mean of absolute blood eosinophils was 197.58 (SD 2.09) cells/μL (range 0 to 3,020). Mean blood eosinophil count was higher in patients with smoking history and frequent exacerbators. At least one moderate and one severe exacerbation occurred in the previous year in 44 and 8% of patients, respectively; during the follow-up year 152 exacerbations were registered, 122 (80%) moderate and 30 (20%) severe. The highest rate of exacerbations in the follow-up year occurred in the subgroup of patients with the frequent exacerbator phenotype and eosinophils ≥300 cells/μL. In this cohort, the frequency of biomass exposure as a risk factor is considerable. High blood eosinophil count was related to smoking, and to the frequent exacerbator phenotype.

Anoctamin pharmacology

TMEM16 proteins, also known as anoctamins, are a family of ten membrane proteins with various tissue expression and subcellular localization. TMEM16A (anoctamin 1) is a plasma membrane protein that acts as a calcium-activated chloride channel. It is expressed in many types of epithelial cells, smooth muscle cells and some neurons. In airway epithelial cells, TMEM16A expression is particularly enhanced by inflammatory stimuli that also promote goblet cell metaplasia and mucus hypersecretion. Therefore, pharmacological modulation of TMEM16A could be beneficial to improve mucociliary clearance in chronic obstructive respiratory diseases. However, the correct approach to modulate TMEM16A activity (activation or inhibition) is still debated. Pharmacological inhibitors of TMEM16A could also be useful as anti-hypertensive agents given the TMEM16A role in smooth muscle contraction.In contrast to TMEM16A, TMEM16F (anoctamin 6) behaves as a calcium-activated phospholipid scramblase, responsible for the externalization of phosphatidylserine on cell surface. Inhibitors of TMEM16F could be useful as anti-coagulants and anti-viral agents. The role of other anoctamins as therapeutic targets is still unclear since their physiological role is still to be defined.

Cigarette smoke-induced dysbiosis: comparative analysis of lung and intestinal microbiomes in COPD mice and patients

BackgroundThe impact of cigarette smoke (CS) on lung diseases and the role of microbiome dysbiosis in chronic obstructive pulmonary disease (COPD) have been previously reported; however, the relationships remain unclear.MethodsOur research examined the effects of 20-week cigarette smoke (CS) exposure on the lung and intestinal microbiomes in C57BL/6JNarl mice, alongside a comparison with COPD patients’ intestinal microbiome data from a public dataset.ResultsThe study found that CS exposure significantly decreased forced vital capacity (FVC), thickened airway walls, and induced emphysema. Increased lung damage was observed along with higher lung keratinocyte chemoattractant (KC) levels by CS exposure. Lung microbiome analysis revealed a rise in Actinobacteriota, while intestinal microbiome showed significant diversity changes, indicating dysbiosis. Principal coordinate analysis highlighted distinct intestinal microbiome compositions between control and CS-exposed groups. In the intestinal microbiome, notable decreases in Patescibacteria, Campilobacterota, Defferibacterota, Actinobacteriota, and Desulfobacterota were observed. We also identified correlations between lung function and dysbiosis in both lung and intestinal microbiomes. Lung interleukins, interferon-ɣ, KC, and 8-isoprostane levels were linked to lung microbiome dysbiosis. Notably, dysbiosis patterns in CS-exposed mice were similar to those in COPD patients, particularly of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 patients. This suggests a systemic impact of CS exposure.ConclusionIn summary, CS exposure induces significant dysbiosis in lung and intestinal microbiomes, correlating with lung function decline and injury. These results align with changes in COPD patients, underscoring the important role of microbiome in smoke-related lung diseases.

Pharmaceutical treatment status of patients with COPD in the community based on medical Internet of Things: a real-world study

This study aimed to investigate the real-world standardisation and adherence of medical treatment regimens in patients with chronic obstructive pulmonary disease (COPD) in the community for making future management strategy. The follow-up data and treatment information of patients with COPD, which were collected through the Management Information Center of COPD (MICCOPD) in 21 community health service centres in Songjiang District, a countryside region of Shanghai. Concordance between the pharmaceutical treatment plan and recommendation of 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report during the follow-up management period, as well as the medication adherence by patients,were analysed. Out of the 2044 patients diagnosed with COPD, 814 patients (39.8%) who had an initial record of medication use were found to meet the inclusion criteria. The most common medication regimens were long-acting beta-agonist plus inhaled corticosteroids (35.9%) and oral bronchodilators (41.9%). Among these 814 patients, 45.7%, 38.0%, 31.6% and 14.6% adhered to the treatment after 6, 12, 18 and 24 months of follow-up, respectively. The concordance rate with the regimens recommended by the 2017 GOLD guidelines was 35.5% at baseline, 35.5% at 6 months, 32.7% at 12 months, 35.4% at 18 months and 37% at 24 months. The compliance and guideline consistency rates of patients with COPD in the community under the management of general practitioners need to be improved. Enhancing general practitioner proficiency in the prevention and management of COPD and increasing patient awareness of the condition, are crucial standardising and improving adherence to initial and follow-up COPD treatments.

Respiratory pathogen and clinical features of hospitalized patients in acute exacerbation of chronic obstructive pulmonary disease after COVID 19 pandemic

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.