Frequent Exacerbations Research Articles

The Effect of Opioids and Benzodiazepines on Exacerbation Rate and Overall Survival in Patients with Chronic Obstructive Pulmonary Disease on Long-Term Non-Invasive Ventilation.

Background: There is a growing concern that opioids and benzodiazepines can depress the respiratory drive and could contribute to worsening respiratory failure and higher exacerbation frequency in COPD. However, the relationship between the exacerbation rate and medication taken is poorly understood in patients with chronic respiratory failure due to COPD. Methods: As part of a service evaluation project, we analysed 339 patients with COPD who were established on long-term non-invasive ventilation (LT-NIV) at our tertiary centre. We investigated the relationship between benzodiazepine and opioid prescription and clinical outcomes as well as their impact on the exacerbation rate and overall survival following setup. Results: Before LT-NIV setup, 40 patients took benzodiazepines and 99 patients took opioids. Neither benzodiazepine nor opioid use was associated with changes in daytime blood gases, overnight hypoxia or annual exacerbations before NIV setup, but patients taking opioids were more breathless as assessed by modified Medical Research Council scores (3.91 ± 0.38 vs. 3.65 ± 0.73, p < 0.01). Long-term NIV significantly reduced the number of yearly exacerbations (from 3.0/2.0-5.0/ to 2.8/0.71-4.57/, p < 0.01) in the whole cohort, but the effect was limited in those who took benzodiazepines (from 3.0/2.0-7.0/ to 3.5/1.2-5.5/) or opioids (3.0/2.0-6.0/ to 3.0/0.8-5.5/). Benzodiazepine use was associated with reduced exacerbation-free survival and overall survival (both p < 0.05). However, after adjustment with relevant covariates, the relationship with exacerbation-free survival became insignificant (p = 0.12). Opioids were not associated with adverse outcomes. Conclusions: Benzodiazepines and opiates are commonly taken in this cohort. Whilst they do not seem to contribute to impaired gas exchange pre-setup, they, especially benzodiazepines, may limit the benefits of LT-NIV.

MANEJO ATUAL DA DOENÇA PULMONAR OBSTRUTIVA CRÔNICA: ABORDAGENSTERAPÊUTICAS E NOVAS PERSPECTIVAS

Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent chronic respiratorycondition characterized by progressive and irreversible airflow limitation. It is associated withsignificant morbidity, with frequent exacerbations that increase hospitalization rates andworsen patients' quality of life. This study reviews the latest therapeutic approaches in COPDmanagement, including pharmacological interventions such as long-acting bronchodilators,inhaled corticosteroids, and biological agents, as well as non-pharmacological strategies suchas smoking cessation and pulmonary rehabilitation. Following an initial search of 6,973studies, 32 articles were reviewed, leading to the inclusion of 9 key studies. The resultsindicate that personalized treatment, combining medications and behavioral interventions,improves lung function and reduces exacerbations. Interventions such as short-durationantibiotic and systemic corticosteroid regimens proved effective in managing acuteexacerbations, while the use of non-invasive ventilation during the COVID-19 pandemic wasshown to be a viable alternative for COPD patients. It is concluded that COPD managementrequires a multidisciplinary and personalized approach to optimize disease control and reducelong-term complications.

Risk Factors Associated with Exacerbation Frequency in Chronic Obstructive Pulmonary Disease

Risk Factors Associated with Exacerbation Frequency in Chronic Obstructive Pulmonary Disease

The Association of Serum Vitamin D Levels with Lung Function, Symptom Severity, and Exacerbations in Stable COPD Patients

Background: Chronic obstructive pulmonary disease (COPD) is a significant health burden associated with a decrease in quality of life. Patients with the disease often have a deficiency of Vitamin D, a fat-soluble vitamin important for respiratory health. A previous study suggested an association between low vitamin D levels and poor lung function, as well as increased exacerbation, and more severe COPD symptom. Therefore, this study aimed to assess serum vitamin D levels in stable COPD patients and explore association with lung function, symptom severity, and frequency of exacerbation. Methods: This was a cross-sectional study conducted from May to July 2023 at Lung Polyclinic of Dr. Zainoel Abidin Regional General Hospital (RSUDZA) Banda Aceh. A total of 30 subjects selected based on specific inclusion and exclusion criteria were included. Results: The results showed that the mean serum vitamin D level was 26.25 ng/mL, with 56.7% of subjects showing vitamin D insufficiency. Statistical analysis showed p-values of 0.58, 0.637, 0.12, and 0.98 for lung function, exacerbation, COPD Assessment Test (CAT), and Modified Medical Research Council (mMRC) dyspnoea scale respectively, indicating no significant association between vitamin D levels and these outcomes. Potential confounding factors include unassessed variables such as medication use, educational background, and psychological status. Conclusion: This study found no significant association between serum vitamin D levels and lung function, symptom severity, or frequency of exacerbation in stable COPD patients. Further studies with a larger sample size and extended follow-up are needed to confirm these results and explore additional influencing factors.

Demographic Data, Risk Factors, and Disease Burden of HS Patients in Lithuania at a Reference Center.

Hidradenitis suppurativa (HS) diagnosis often faces a global delay of 7.2 years due to factors like lack of recognition, stigma, and socioeconomic barriers. Limited effective therapies and frequent exacerbations impact patients' quality of life, posing a significant burden on healthcare systems. HS patients were assessed according to European Hidradenitis Suppurativa Foundation (EHSF) Registry questionnaire guidelines at various stages of the disease and treatment. The study included 49 patients; 57.14% (n = 28) of them were male. The average age of the subjects was 39.91 ± 13.665 years; the average BMI was 27.84 ± 7.362. A total of 59.18% (n = 29) were active or previous smokers. There were statistically more male smokers than female (p < 0.01). Average disease onset was 25.71 ± 13.743 years; the mean time to diagnosis was 5.2 ± 7.607 years. A total of 70.2% (n = 33) were previously misdiagnosed. Subjects had 6.17 ± 6.98 painful days over the preceding 4 weeks. The average intensity of pain according to the visual analogue scale (VAS) was 5.60 ± 3.36 points. The mean dermatology life quality index (DLQI) at baseline was 8.9 ± 7.436. The research revealed delayed diagnoses, especially for females. Smoking was linked to higher Hurley stages, with a prevalence among male smokers, and HS had a substantial impact on patients' quality of life.

Prevalence of and factors associated with cognitive frailty in elderly patients with chronic obstructive pulmonary disease: A cross-sectional study.

The status of cognitive frailty in elderly patients with chronic obstructive pulmonary disease (COPD) and its influencing factors in China remains unclear. This study aimed to investigate the prevalence of and factors associated with cognitive frailty in elderly patients with COPD. This cross-sectional study enrolled elderly patients with stable COPD between May and November 2022 from the Respiratory Department of the First Affiliated Hospital of Zhengzhou University and the Fifth Affiliated Hospital of Zhengzhou University. Convenience sampling method was adopted. Frailty Phenotype scale, Montreal Cognitive Assessment scale, Geriatric Depression Scale, and Clinical Dementia Rating scale were used to assess the prevalence of cognitive frailty in elderly patients with COPD. Multivariable logistic regression analysis was used to explore the associated factors. A total of 406 valid questionnaires were collected, and 173 patients (35.6%) had cognitive frailty. Binary logistic regression analysis showed that sex (odds ratio [OR] = 0.009; 95%CI: 0.001-0.770; P = .038), depression (OR = 17.780; 95%CI: 1.092-289.478; P = .043), modified Medical Research Council grade 1-3 (OR = 28.394-4095.683; 95%CI: 1.086-4,592,652.211; P < .05), global initiative for chronic obstructive lung disease grade 2 and 3 (OR = 32.508-282.072; 95%CI: 1.101-12,516.874; P < .05), and frequencies of acute exacerbations of COPD and hospitalizations within 1 year of 2 times (OR = 21.907; 95%CI: 4.587-104.622; P < .001) were independently associated with cognitive frailty. The prevalence of cognitive frailty in elderly patients with stable COPD was high. Female, depression, modified Medical Research Council grade, global initiative for chronic obstructive lung disease grade, and frequencies of acute exacerbations of COPD and hospitalizations within 1 year might be the factors independently associated with cognitive frailty, educational level might be a protective associated factor for cognitive frailty.

Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF®, a Phase II randomised, double-blind, placebo-controlled, dose-finding study.

Bronchiectasis is characterised by uncontrolled neutrophil serine protease (NSP) activity. Cathepsin C (CatC; dipeptidyl peptidase 1) activates NSPs during neutrophil maturation. CatC inhibitors can potentially reduce neutrophil-mediated lung damage. This Phase II, randomised, double-blind, placebo-controlled trial (AIRLEAF®; NCT05238675) evaluated efficacy, safety and optimal dosing of BI 1291583, a novel, reversible CatC inhibitor, in adults with bronchiectasis.In total, 322 participants were randomised (2:1:1:2) to receive one of three oral doses of BI 1291583 (1 mg/2.5 mg/5 mg) or placebo for 24 to 48 weeks. A multiple comparison procedure and modelling approach was used to demonstrate a non-flat dose-response curve based on the time to first pulmonary exacerbation up to Week 48. In addition, efficacy of individual BI 1291583 doses was evaluated based on the frequency of exacerbations, severe exacerbations (fatal or leading to hospitalisation and/or intravenous antibiotic administration), lung function and quality of life.A significant dose-dependent benefit of BI 1291583 over placebo was established based on time to first exacerbation (shape: Emax; adjusted p-value: 0.0448). Treatment with BI 1291583 5 mg and 2.5 mg numerically reduced the risk of an exacerbation compared with placebo (hazard ratios: 0.71 and 0.66, 95% CIs 0.48-1.05 and 0.40-1.08; both p>0.05). BI 1291583 2.5 mg showed numerically better efficacy compared with 5 mg across several endpoints; 1 mg was similar to placebo. The safety profile of BI 1291583 was similar to placebo.Treatment with BI 1291583 resulted in a reduction in the risk of experiencing an exacerbation in adults with bronchiectasis.

Methodology for the selection and evaluation of outcomes for Chinese herbal injection in acute exacerbation of chronic obstructive pulmonary disease (AECOPD): a comprehensive study

Objective To develop a comprehensive framework for selecting outcomes in evaluating the clinical efficacy of Chinese herbal injections and to scientifically select outcomes for the clinical randomized controlled trial (RCT) of Tan-Re-Qing injection intervening AECOPD. Methods A comprehensive literature review and consensus methods, including focus groups and Delphi surveys, were utilized. Results Literature analysis identified 513 publications, encompassing regulatory guidance, guidelines, expert consensus, and RCTs. Initial dimensions include clinical efficacy, safety, and health economics. Primary outcomes should align with study objectives. Recommended evaluation domains include death, treatment outcome, future impact, quality of life, and safety. Commonly recommended outcomes comprise mortality, arterial blood gases, CAT, exacerbation frequency, adverse events, and lung function. Network meta-analysis identified specific therapeutic efficacy markers (white blood cell count, IL-6, IL-8). Quality of life assessment recommended SF-12, EQ-5D, or CAT. Emphasis on AECOPD frequency and lung function was noted. Delphi survey yielded 41 outcomes across various domains for evaluating Tan-Re-Qing in AECOPD. Conclusion The findings contribute to developing a robust and reliable trial design for Tan-Re-Qing injection in AECOPD. The methodology employed in this study ensures a systematic and comprehensive approach to the selection of outcomes for the clinical evaluation of future studies in this field.

A comparison of the impact of anti-IL5/5r therapies in allergic versus non-allergic patients with severe eosinophilic asthma in a real-life setting

Objective This study aimed to compare the clinical characteristics and treatment outcomes of allergic patients (AP) and non-allergic patients (NAP) with severe eosinophilic asthma (SEA) treated with anti-IL5/IL5R biologic agents (mepolizumab, benralizumab, or reslizumab) over one year. Sub-analyses assessed treatment response variations between AP and NAP based on the biological used and compared outcomes among AP with and without fungal allergy. Methods Observational retrospective analysis. Clinical characteristics, laboratory findings, pulmonary function tests, Asthma Control Test (ACT) scores, oral corticosteroid (OCS) usage, and exacerbation frequency were assessed at the initiation of biological treatment and after one year. Results Sixty-five patients with SEA were included, 41 AP and 24 NAP. 55.4% were treated with mepolizumab, 33.8% with benralizumab, and 10.8% with reslizumab. Before anti-IL5/5R treatment, AP had worse baseline outcomes but there were no differences in pulmonary function. Mean annual exacerbation rate and percentage of patients requiring OCS and dose of prednisone were higher in AP than NAP. AP had significantly higher total IgE values. After one year of treatment, more AP discontinued OCS than NAP (p = 0.025). Both experienced a significant reduction in exacerbation frequency (p = 0.001) and improved respiratory function. 70.7% of AP and 60% of NAP improved ACT ≥3 points. There was no significant difference between AP and NAP using mepolizumab (p = 0.145) or benralizumab (p = 0.174) in reducing OCS. Conclusions Anti-IL5/IL5R reduced the need for OCS and improved asthma control, regardless of allergic status. Fungal allergy led to lower ACT scores and higher exacerbations than other allergens; both groups improved with anti-IL5/ILR.

Drugs for COPD.

The main goals of treatment of chronic obstructive pulmonary disease (COPD) are to relieve symptoms, reduce the frequency and severity of exacerbations, prevent disease progression, and reduce mortality. GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines for treatment of COPD were updated recently.1 Treatment of acute exacerbations is not discussed here. Drugs available for treatment of COPD are listed in Tables 1 and 3.

Self-report underestimates the frequency of the acute respiratory exacerbations of COPD but is associated with BAL neutrophilia and lymphocytosis: an observational study

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

Immediate and One-Year Outcomes of an Asthma-Tailored Pulmonary Rehabilitation Programme in Overweight and Obese People with Difficult-to-Treat Asthma.

Management of difficult-to-treat asthma is particularly challenging in people with elevated body mass index (BMI). Our randomised controlled trial of pulmonary rehabilitation (PR) showed improved outcomes at 8weeks. Here we assess immediate and one-year effects of asthma-tailored PR in participants with difficult-to-treat asthma and BMI ≥25 kg/m2, and identify response predictors. A prospective observational study of PR, tailored to asthma, comparing outcomes at baseline (V1), immediately after 8 weeks of PR (V2), and at 1 year (V3). Baseline characteristics were compared in responders/non-responders defined by achievement of minimum clinically important difference (MCID) for asthma control questionnaire (ACQ6) (0.5) at 8weeks and 1 year. Of 92 participants, 56 attended V2 and 45 attended V3. Mean age was 60 (SD 13) years, 60% were female, and median (IQR) BMI was 33.8 (29.5-38.7) kg/m2. At V1, V2, and V3, respectively, there were significant differences in ACQ6 (mean (95% CI): 2.5 (2.1-2.9), 2.2 (1.8-2.5), and 2.3 (1.9-2.7), p<0.003), Borg breathlessness score post-6-minute walk test (median (IQR): 2 (0.5-3), 1 (0-2), and 1 (0.5-2), p<0.035), and annualised exacerbations requiring prednisolone (median (IQR): 3 (2-5), 0 (0-4.7), and 1.5 (0-4.2), p<0.003). A total of 27/56 (48%) had improvements >MCID for ACQ6 at V2 and 16 (33%) at V3. Participants with higher ACQ6 scores at baseline (suggesting poorer asthma control) were more likely to achieve MCID. Baseline BMI, within the range studied, was not predictive. Pulmonary rehabilitation induced improvements in asthma-related outcomes including perception of breathlessness, asthma control, and exacerbation frequency at 1 year. Those with poorer baseline asthma control were more likely to benefit.

Long-Term Clinical Efficacy of Elexacaftor-Tezacaftor-Ivacaftor in People With Cystic Fibrosis and Preexisting Advanced Lung Disease at Treatment Initiation

BackgroundElexacaftor-tezacaftor-ivacaftor (ETI) is associated with increased forced expiratory volume in the first second (FEV1), decreased exacerbation frequency, and increased body mass index (BMI) in people with Cystic Fibrosis (pwCF) [1, 2]. Landmark clinical trials excluded patients with advanced lung disease (ALD) as defined by FEV1<40%. We have previously reported an improvement in ppFEV1 of 7.9% after 3 months of ETI in people with CF and ALD (ACFLD)[3]. The long-term effects of ETI on this cohort are unknown. This study reports the efficacy of ETI following 24 months of treatment in people with ACFLD. Study DesignWe conducted a retrospective cohort study of adult patients with FEV1<40% and/or other high-risk features defined by the 2019 CFF lung transplant guidelines who were started on ETI between September 2019 and February 2020. Response to therapy was assessed with repeat spirometry measured at 12 and 24 months. All measurements were taken outside of an acute exacerbation. Demographics and clinical data including BMI and pulmonary exacerbation frequency were extracted from the medical record. Results57 of 64 people with ACFLD showed improved lung function with a mean change in ppFEV1 of 6.74% (p = <0.001, 95% CI 4.25 – 9.23%) between baseline and 24 months of treatment. BMI increased by a mean change of 1.55 kg/m2 (p = <0.001, 95% CI 0.93 – 2.18 kg/m2) during this interval. The annual exacerbation rate between the year before ETI and 24 months on ETI declined with a median of 1 fewer per year (p = 0.0007). InterpretationPeople with ACFLD experienced a significant increase in lung function at 24 months on ETI, although less than those with higher baseline lung function compared to prior studies [1, 2]. They also had an increase in BMI and a decline in the rate of annual pulmonary exacerbations.

CLINICAL MANAGEMENT OF CHRONIC ORANGUTAN RESPIRATORY DISEASE SYNDROME IN THREE ADULT MALE BORNEAN ORANGUTANS (PONGO PYGMAEUS).

Orangutan respiratory disease syndrome (ORDS) is a disease unique to orangutans (Pongo sp), characterized by chronic bacterial infection and inflammation of any region or combination of regions of the respiratory tract, including the sinuses, air sacs, cranial bones, airways, and lung parenchyma. Aggressive early intervention during a first episode may prevent progression to chronic disease. However, in the setting of an established chronic disease, intermittent acute exacerbations are associated with worsening symptoms and increased infection and inflammation. ORDS is ultimately fatal due to loss of respiratory function resulting from chronic structural damage. Utilizing potentially lifelong medications to slow the progression of chronic, destructive inflammation in the respiratory tract, chronic treatment is aimed at stabilizing the animals' respiratory function, decreasing the frequency of recurrent exacerbations, and improving their general well-being. Three adult male Bornean orangutans (Pongo pygmaeus) housed at an orangutan rehabilitation and reintroduction center in Indonesia have long histories of recurrent respiratory disease. Each underwent CT scans confirming ORDS with chronic airway disease prior to initiation of a long-term treatment protocol. Based on data-driven medical management of bronchiectasis in humans, the three orangutans have been treated with long-term combination regimens of oral azithromycin, nebulized salbutamol, and nebulized hypertonic saline. Follow-up CT scans in all three animals at least 1 yr following treatment initiation showed improvements throughout their respiratory tracts. The duration of each exacerbation period decreased, and the orangutans have longer symptom-free periods compared to before the start of treatment. At an average of 5 yr into the long-term treatment protocol, all three orangutans are thriving. Chronic medical management of ORDS modeled after human treatment of bronchiectasis has been efficacious in these three orangutans and encourages further study of this approach.

The Clinical Characteristics, Treatment and Prognosis of Tuberculosis-Associated Chronic Obstructive Pulmonary Disease: A Protocol for a Multicenter Prospective Cohort Study in China.

Tuberculosis and chronic obstructive pulmonary disease (COPD) are significant public health challenges, with pulmonary tuberculosis recognized as a pivotal risk factor for the development of COPD. Tuberculosis-associated COPD is increasingly recognized as a distinct phenotype of COPD that potentially exhibits unique clinical features. A thorough understanding of the precise definition, clinical manifestations, prognosis, and most effective pharmacological strategies for tuberculosis-associated COPD warrants further investigation. This prospective, observational cohort study aims to enroll over 135 patients with tuberculosis-associated COPD and 405 patients with non-tuberculosis-associated COPD, across seven tertiary hospitals in mainland China. The diagnosis of tuberculosis-associated COPD will be established based on the following criteria: (1) history of pulmonary tuberculosis with standard antituberculosis treatment; (2) suspected pulmonary tuberculosis with radiological evidence indicative of tuberculosis sequelae; (3) no definitive history of pulmonary tuberculosis but with positive interferon-gamma release assay results and radiological signs suggestive of tuberculosis. At baseline, demographic information, medical history, respiratory questionnaires, complete blood count, interferon-gamma release assays, medications, spirometry, and chest computed tomography (CT) scans will be recorded. Participants will be followed for one year, with evaluations at six-month intervals to track the longitudinal changes in symptoms, treatment, lung function, and frequencies of COPD exacerbations and hospitalizations. At the final outpatient visit, additional assessments will include chest CT scans and total medical costs incurred. The findings of this study are expected to delineate the specific characteristics of tuberculosis-associated COPD and may propose potential treatment options for this particular phenotype, potentially leading to improved clinical management and patient outcomes.

Implications of Global Lung Function Initiative Spirometry Reference Equations in Northeast Asian Patients With COPD

Accurate spirometry interpretation is critical in the diagnosis and management of chronic obstructive pulmonary disease (COPD). With increasing efforts for a unified approach by the Global Lung Function Initiative (GLI), this study evaluated the application of race-specific 2012-GLI and race-neutral 2022-GLI reference equations compared to Choi's reference equations, which is derived and widely used in South Korea, for spirometry interpretation in Northeast Asian patients with COPD. What are the effects of applying race-specific 2012-GLI, race-neutral 2022-GLI, and Choi's reference equations on the diagnosis, severity grade, and clinical outcome associations of COPD STUDY DESIGN AND METHODS: Serial spirometry data from the Korea COPD Subgroup Study (KOCOSS) consisting of 3,477 patients were utilized for re-analyses using 2012-GLI, 2022-GLI, and Choi's reference equations. The COPD diagnosis and severity categorization, associations with disease manifestations and health outcomes, and longitudinal trajectories of lung function were determined. Although there was strong concordance in COPD diagnosis comparing 2012-GLI, and 2022-GLI reference equations to Choi's reference equations, a notable portion of patients were reclassified to milder disease severity (17.0% and 23.4% for 2012-GLI and 2022-GLI reference equations, respectively). Relationships between FEV1 percent-predicted values calculated using 2012-GLI, 2022-GLI, and Choi's equations with clinical outcomes including dyspnea severity, exercise capacity, health-related quality of life, and frequency of exacerbations remain consistently significant. Similar annual decline rates of FEV1 and FVC percent-predicted were observed among the reference equations used, except for slower annual decline rate of FEV1 in Choi's equation compared to 2022-GLI race-neutral equation. Application of GLI reference equations for spirometry interpretation in Northeast Asian patients with COPD has potential implications on disease severity grade for clinical management and trial participation, and maintains consistent significant relationships with key disease outcomes.

Low-dose azithromycin prophylaxis in patients with atrial fibrillation and chronic obstructive pulmonary disease.

Low-dose azithromycin prophylaxis is associated with improved outcomes in people suffering frequent exacerbations of chronic obstructive pulmonary disease (COPD), but the use of macrolides in patients with cardiovascular disease has been debated. To investigate the risk of adverse events after COPD exacerbations in patients with atrial fibrillation (AF) treated with azithromycin prophylaxis. Retrospective cohort study within the TriNetX Platform, including AF patients with COPD exacerbations. Risks of primary and secondary outcomes were recorded up to 30days post-COPD exacerbations and compared between azithromycin users and azithromycin non-users. The primary outcomes were the risks for a composite of (1) cardiovascular (all-cause death, heart failure, ventricular arrhythmias, ischemic stroke, myocardial infarction, and cardiac arrest), and (2) hemorrhagic events (intracranial hemorrhage (ICH), and gastro-intestinal bleeding). Cox-regression analyses compared outcomes between groups after propensity score matching (PSM). After PSM, azithromycin users (n = 2434, 71 ± 10years, 49% females) were associated with a lower 30-day risk of post-exacerbation cardiovascular (HR 0.67, 95% CI 0.61-0.73) and hemorrhagic composite outcome (HR 0.45, 95% CI 0.32-0.64) compared to azithromycin non-users (n = 2434, 72 ± 11years, 51% females). The beneficial effect was consistent for each secondary outcomes, except ICH. On sensitivity analyses, the reduced risk of adverse events in azithromycin users was irrespective of smoking status, exacerbation severity, and type of oral anticoagulation. Azithromycin prophylaxis is associated with a lower risk of all-cause death, thrombotic and hemorrhagic events in AF patients with COPD. The possible role of azithromycin prophylaxis as part of the integrated care management of AF patients with COPD needs further study.

Adapting the cystic fibrosis care model: Perspectives from people with CF, caregivers, and members of CF care teams.

Rapidly emerging clinical trends offer the opportunity to amend guidance on issues pertaining to CF care delivery. A national survey was conducted to gather perspectives on CF care including potential adaptations to the care model to best meet the needs of this population. A survey instrument was developed to capture perspectives on CF care. People with CF (pwCF), including those post lung transplant, caregivers and care teams were surveyed. Descriptive statistics were calculated to characterize respondents and responses. In-person, routine visits with the CF care teams were valued by survey respondents. However, reduced in-person visit frequency from the standard three-month interval was supported for individuals in a stable state of health. This was particularly true for pwCF ages two or older and on a modulator. Lung function, pulmonary exacerbation frequency, and transition periods were noted to influence preference for visit frequency. Integrating telehealth with remote monitoring in between visits was broadly supported. For shared care between CF teams and other medical providers (transplant teams and primary care providers (PCP)), good communication, easily accessible health records, and convenient locations were important. Survey findings support adapting CF care based on individual needs and life transitions. Themes identified can inform future areas of study and resource development to support successful modification of the CF care model and shared decision-making between patients and their care providers.

Effects of the teach-back method on the health status of patients with chronic obstructive pulmonary disease: a real-world community-based cluster-randomized controlled trial.

The teach-back method (TBM), also known as the "show-me" method, is a technique for verifying patients' understanding of health-related information that has been recommended for improving health literacy. However, the research on TBM effect on the outcomes of chronic obstructive pulmonary disease (COPD) patients is limited. Therefore, the aim of this study was to examine the effect of a TBM intervention on the health status of COPD patients. This real-world community-based cluster-randomized controlled trial enrolled 1,688 patients with COPD from 18 communities in China. Participants received either TBM plus usual care (UC) or UC only. General practitioners were trained in TBM before the intervention. The primary outcomes were depression and anxiety symptoms, as measured by the Hospital Anxiety and Depression Scale (HADS). The secondary outcomes were health-related quality of life and dyspnea, as measured by the COPD Assessment Test (CAT). Dyspnea was assessed using the modified Medical Research Council (mMRC) dyspnea scale. Data on acute exacerbations and deaths were extracted from medical records. Lung function was expressed as the forced expiratory volume in 1 second as a percentage of the predicted value [FEV1 (% pred)]. In total, 336 of the 853 COPD patients in the intervention group (TBM plus UC) had comorbid depression, compared with 329 of the 835 in the control group (UC only). The TBM group showed a significantly greater improvement in HADS depression and anxiety subscale scores (HADS-D and HADS-A, respectively) than the UC group at12 months (t =8.34, P<0.001; t=12.18, P<0.001). The CAT and mMRC scores were significantly lower in the TBM than UC group at 12 months (t=8.43, P<0.001; t=7.23, P<0.001). The numbers of acute exacerbations and deaths were significantly lower in the TBM than UC group at 12 months (mean MCF values were 0.35 and 0.56, respectively [difference of 0.22; 95% confidence interval (CI): -0.41, -0.02; χ2=9.63, P<0.001]. The FEV1 (% pred) was significantly higher in the TBM than UC group at 12 months (t=7.45, P<0.001). General practitioners can use TBM interventions to effectively reduce anxiety, depression, and dyspnea symptoms, decrease the frequency of exacerbations and likelihood of death, and improve health-related quality of life and pulmonary function in patients with COPD. The trial was registered on the Chinese Clinical Trials Registry (reference: ChiCTR-TRC-12001958).

Clinical immunological characteristics of anti-interferon-γ autoantibodies syndrome: a 3 year prospective cohort study

ABSTRACT Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.