Frequent Exacerbations Research Articles

Lung Structure and Risk of Sleep Apnea in SPIROMICS.

The SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) is a prospective cohort study that enrolled 2981 participants with the goal of identifying new chronic obstructive pulmonary disease (COPD) subgroups and intermediate markers of disease progression. Individuals with COPD and obstructive sleep apnea (OSA) experience impaired quality of life and more frequent exacerbations. COPD severity also associates with computed tomography scan-based emphysema and alterations in airway dimensions. The objective was to determine whether the combination of lung function and structure influences the risk of OSA among current and former smokers. Using 2 OSA risk scores, the Berlin Sleep Questionnaire (BSQ), and the DOISNORE50 (Diseases, Observed apnea, Insomnia, Snoring, Neck circumference > 18 inches, Obesity with body mass index [BMI] > 32, R = are you male, Excessive daytime sleepiness, 50 = age ≥ 50) (DIS), 1767 current and former smokers were evaluated for an association of lung structure and function with OSA risk. The study cohort's mean age was 63 years, BMI was 28 kg/m2, and forced expiratory volume in 1 second (FEV1) was 74.8% predicted. The majority were male (55%), White (77%), former smokers (59%), and had COPD (63%). A high-risk OSA score was reported in 36% and 61% using DIS and BSQ respectively. There was a 9% increased odds of a high-risk DIS score (odds ratio [OR]=1.09, 95% confidence interval [CI]:1.03-1.14) and nominally increased odds of a high-risk BSQ score for every 10% decrease in FEV1 %predicted (OR=1.04, 95%CI: 0.998-1.09). Lung function-OSA risk associations persisted after additionally adjusting for lung structure measurements (%emphysema, %air trapping, parametric response mapping for functional small airways disease, , mean segmental wall area, tracheal %wall area, dysanapsis) for DIS (OR=1.12, 95%CI:1.03-1.22) and BSQ (OR=1.09, 95%CI:1.01-1.18). Lower lung function independently associates with having high risk for OSA in current and former smokers. Lung structural elements, especially dysanapsis, functional small airways disease, and tracheal %wall area strengthened the effects on OSA risk.

Very long-term data on patients with severe eosinophilic asthma treated with mepolizumab: a case series.

Patients with severe asthma are often dependent on oral corticosteroids (OCS) and have frequent exacerbations. This article aims to report very long-term data of patients with severe eosinophilic asthma assessing asthma control, lung function, inhaled corticosteroid (ICS) dose reduction, and clinical and biological parameters of patients treated with mepolizumab. Four cases of adult patients with severe eosinophilic asthma who were treated for 60 months or more with mepolizumab 100 mg/4 weeks, leading to the stable discontinuation of OCS, are presented. ICS dose, OCS dose and withdrawal date, lung function, eosinophil count, fractional exhaled nitric oxide, and asthma control test were recorded as well as exacerbations in the 12 months before commencing mepolizumab and in the 12 months before the last follow-up visit. Three of the patients were men, median age was 52.5 years (range 79-53), median length of asthma before mepolizumab start was 67.5 months (range 24-240), three had chronic rhinosinusitis without nasal polyposis and two were atopic. All had eosinophil counts >300 cells/μL at baseline. The median follow-up was 73.5 months (range 71-74), and OCS withdrawal from baseline occurred after a median of 13 months of mepolizumab treatment (range 12-39). A substantial reduction of ICS treatment was registered as well as improvement in asthma control test, fractional exhaled nitric oxide and functional parameters, and a significant reduction of exacerbations in the last 12 months before last visit was observed as compared to the 12 months before baseline (from a median of 4 (range 3-6) to 0; p=0.0286). Mepolizumab could be a 'disease-modifying' agent, with high tolerability and a good efficacy profile in the long term.

Bacteria and viruses and clinical outcomes of asthma-bronchiectasis overlap syndrome: A cohort study.

Despite the high prevalence of co-existing bronchiectasis and asthma (asthma-bronchiectasis overlap syndrome [ABOS]), little is known regarding the dominant pathogens and clinical correlates. To investigate the bacteria and viruses which differentially dominate in ABOS (including its subtypes) compared with bronchiectasis alone, and determine their relevance with bronchiectasis severity and exacerbations. This was a prospective observational cohort study conducted between March 2017 and August 2023. We included 81 patients with ABOS and 107 patients with bronchiectasis alone. At steady-state baseline, patients underwent comprehensive assessments and sputum collection for bacterial culture and viral detection (quantitative polymerase-chain-reaction). Patients were followed-up to record exacerbation and spirometry. Patients with ABOS had significantly higher symptom burden and exacerbation frequency than those with bronchiectasis alone. Despite similar pathogen spectrum, the rate of bacteria-virus co-detection increased less substantially at acute exacerbations (AE) onset than at steady-state compared with bronchiectasis alone. Pathogenic bacteria (particularly Pseudomonas aeruginosa) were detected fairly common (exceeding 50%) in ABOS and were associated with greater severity of bronchiectasis when stable and conferred greater exacerbation risks at follow-up. Viral but not bacterial compositions changed substantially at AE onset compared with clinical stability. Higher blood eosinophil count, moderate-to-severe bronchiectasis and non-atopy were associated with higher odds of bacterial, but not viral, detection (all p<0.05). Detection of bacteria or virus is associated with bronchiectasis severity or clinical outcomes in ABOS. This highlights the importance of integrating sputum microbial assessment for ascertaining the dominant pathophysiology (atopy vs. infection) and longitudinal trajectory prediction in ABOS.

Hypertonic saline inhalation therapy among patients with moderate asthma and functional dyspepsia commorbidity

Aim: Dry powder hypertonic saline inhalation use possibilities evaluation in moderate asthma and functional dyspepsia patients. Materials and Methods: 68 moderate asthma and functional dyspepsia patients were examined and treated according to the standard protocols, serum and erythrocytes membrane fatty acid levels were evaluated. The groups of patients with (n=35) and without (n=33) additional dry powder hypertonic saline inhalation use were compared after 1 month. Results: After additional use of dry powder hypertonic saline inhalations vs only standard treatment the rate of well controlled asthma was 3 fold higher with significantly higher FEV1. We also observed positive dynamics of serum arachidonic and docosahexaenoic acids levels indicating resolution of inflammatory reaction with erythrocytes membranes linoleic acid level normalization (source of antiinflammatory cytokines synthesis) among patients with dry powder hypertonic saline inhalation use vs without it. Among patients who used only standard therapy compared to the control group, the erythrocytes membrane linoleic acid level remained decreased with high serum arachidonic and docosahexaenoic acids levels. Follow-up results (after 1 year) showed a significant decrease in exacerbations frequency among patients who underwent dry powder hypertonic saline inhalation vs only the standard treatment. Conclusions: Among moderate asthma patients with functional dyspepsia use of dry powder hypertonic saline inhalation therapy additionally to the standard treatment allows to improve not only clinical and functional parameters but serum and erythrocytes membranes fatty acids spectrum as well leading to the systemic inflammatory reaction reduction and exacerbations prevention in remote period.

Efficacy and safety of Cordyceps sinensis (Hirsutella sinensis, Cs-C-Q80) in chronic bronchitis.

Background: Cordyceps sinensis is a traditional Chinese medicine that has shown promise for the management of chronic bronchitis (CB). We aim to assess the efficacy and safety of a preparation of C sinensis named Bailing capsule (Hirsutella sinensis, Cs-C-Q80) compared with a placebo in patients with CB. Methods: This randomized, double-blind, placebo-controlled, parallel-group clinical trial (Chinese Clinical Trial Registry; registration number: ChiCTR1900025707) recruited patients with CB from eight hospitals in China between May 2019 and December 2020. Patients were randomized 2:1 to receive Bailing capsule or a placebo orally for 48weeks (2.0g, three times a day). Results: Among 240 patients who were randomized, 238 (Bailing capsule: 159, placebo: 79) were included in the primary analysis. Bailing capsule significantly reduced the frequency of acute exacerbation of CB (AECB) compared with the placebo during treatment (0.43 ± 0.82 vs. 1.56 ± 1.34; P < 0.001) and follow-up (0.21 ± 0.64 vs. 0.45 ± 0.93; P = 0.026). Bailing capsule improved the severity of expectoration (P = 0.046) and wheezing (P = 0.010) in AECB during follow-up. The severity of CB after treatment was significantly improved in the Bailing capsule group compared with the placebo group (P = 0.035), particularly in terms of expectoration (P = 0.012) and wheezing (P = 0.003). The risk of adverse events, mainly including infectious and invasive diseases and gastrointestinal symptoms, did not significantly differ between the two groups (29.6% vs. 30.4%). Conclusion: In patients with CB, Bailing capsule significantly reduces the frequency of AECB and ameliorates the severity of AECB and CB symptoms. Clinical Trail Registration: https://www.chictr.org.cn, identifer ChiCTR1900025707.

Clinical Characteristics and Frequency of Chronic Obstructive Pulmonary Disease Exacerbations in Korean Patients: Findings From the KOCOSS Cohort 2012-2021.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) exert a substantial burden on patients and healthcare systems; however, data related to the frequency of AECOPD in the Korean population are limited. Therefore, this study aimed to describe the frequency of severe, and moderate or severe AECOPD, as well as clinical and demographic characteristics of patients with chronic obstructive pulmonary disease (COPD) in South Korea. Data from patients aged > 40 years with post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ≤ 70% of the normal predicted value from the Korea COPD Subgroup Study database were analyzed (April 2012 to 2021). The protocol was based on the EXAcerbations of COPD and their OutcomeS International study. Data were collected retrospectively for year 0 (0-12 months before study enrollment) based on patient recall, and prospectively during years 1, 2, and 3 (0-12, 13-24, and 25-36 months after study enrollment, respectively). The data were summarized using descriptive statistics. Data from 3,477 Korean patients (mean age, 68.5 years) with COPD were analyzed. Overall, most patients were male (92.3%), former or current smokers (90.8%), had a modified Medical Research Council dyspnea scale score ≥ 1 (83.3%), and had moderate airflow limitation (54.4%). The mean body mass index (BMI) of the study population was 23.1 kg/m², and 27.6% were obese or overweight. Hypertension was the most common comorbidity (37.6%). The mean blood eosinophil count was 226.8 cells/μL, with 21.9% of patients having ≥ 300 cells/μL. A clinically insignificant change in FEV1 (+1.4%) was observed a year after enrollment. Overall, patients experienced a mean of 0.2 severe annual AECOPD and approximately 1.1 mean moderate or severe AECOPD. Notably, the rates of severe AECOPD remained generally consistent over time. Compared with patients with no exacerbations, patients who experienced severe exacerbations had a lower mean BMI (21.7 vs. 23.1 kg/m²; P < 0.001) and lower lung function parameters (all P values < 0.001), but reported high rates of depression (25.5% vs. 15.1%; P = 0.044) and anxiety (37.3% vs. 16.7%; P < 0.001) as a comorbidity. Findings from this Korean cohort of patients with COPD indicated a high exacerbation burden, which may be attributable to the unique characteristics of the study population and suboptimal disease management. This highlights the need to align clinical practices with the latest treatment recommendations to alleviate AECOPD burden in Korea. ClinicalTrials.gov Identifier: NCT05750810.

Characteristics of Severe Asthma in the Elderly: Observations From the Korean Severe Asthma Registry (KoSAR).

Few studies have compared the clinical characteristics of severe asthma (SA) in elderly patients compared to that in nonelderly patients. We analyzed data from the Korean SA Registry, a nationwide, real-world observational study of SA in Korea. The baseline clinical characteristics, disease control status, and medication use of the patients were compared between elderly (≥ 65 years) and nonelderly groups. Of the 864 patients with SA, 260 (30.1%) were in the elderly group. The elderly group had lower atopy rate, but had higher prevalence of chronic obstructive pulmonary disease (COPD), hypertension, and osteoporosis than did the nonelderly group. The elderly group had a lower rate of type 2 inflammation and lower levels of forced expiratory volume in 1 second (FEV1) (% predicted) and FEV1/forced vital capacity ratio than did the nonelderly group (P < 0.05 for all). However, asthma symptom scores and the frequency of asthma exacerbation were not significantly different between the 2 groups. Of controller medications, biologics were less frequently used in the elderly group (P < 0.05 for all). SA in the elderly is characterized by lower lung function, less type 2-low airway inflammation, and comorbidity with COPD. These findings are being taken into consideration in the management of elderly patients with SA in real-world clinical practice.

Multimorbidities in COPD are Associated With Increased Exacerbations and Health Care Resource Utilization in Real-World Patients from a U.S. Database.

Patients with chronic obstructive pulmonary disease (COPD) often develop other morbidities, suggesting a systemic component to this disease. This retrospective noninterventional cohort study investigated relationships between multimorbidities in COPD and their impact on COPD exacerbations and COPD-related health care resource utilization (HCRU) using real-world evidence from Optum's de-identified Clinformatics® Data Mart Database. Demographic and clinical characteristics were assessed. Overall comorbidity burden and proportion of individuals with gastroesophageal reflux disease (GERD), diabetes, or osteoporosis/osteopenia were compared in age-matched COPD versus non-COPD cohorts using descriptive statistics. COPD exacerbations and COPD-related HCRU (hospitalizations and emergency department visits) were compared between age-matched cohorts of COPD patients with and without specific common morbidities (GERD, diabetes, and osteoporosis/osteopenia). Additional weight-matching was performed for matched cohorts of COPD patients with and without diabetes, and with and without osteoporosis/osteopenia. The follow-up period was 5 years. Age-matched cohorts with and without COPD each comprised 158,106 patients. Morbidities were more common in the COPD cohort than the cohort without COPD (GERD: 44.9% versus 27.8%; diabetes: 40.8% versus 31.1%; osteoporosis/osteopenia: 18.8% versus 14.1%, respectively). Compared with matched cohorts with COPD only, cohorts of COPD patients with either GERD, diabetes, or osteoporosis/osteopenia experienced increased risk of severe exacerbations (odds ratio [OR]=1.819, OR=1.119, and OR=1.373, respectively), moderate exacerbations (OR=1.699, OR=1.102, and OR=1.322, respectively), or any exacerbations (OR=1.848, OR=1.099, and OR=1.384, respectively, p<0.001 for all comparisons) and increased risk of COPD-related HCRU (emergency department visits: OR=1.983, OR=1.098, and OR=1.343, respectively; hospitalization visits: OR=2.222, OR=1.26, and OR=1.368, respectively; p<0.001 for all comparisons). These real-world data confirm that GERD, diabetes, and osteoporosis are common morbidities in patients with COPD and, moreover, that they affect frequency of exacerbation and HCRU. Determining and addressing the mechanisms behind the systemic effects of COPD may be beneficial for COPD patients and may also help reduce COPD exacerbations.

Experience in the use of cladribine for the treatment of patients with highly active forms of multiple sclerosis in the Moscow region

To assess the efficacy and safety of cladribine in patients with highly active multiple sclerosis (MS) in the Moscow region. The analysis was based on data from 62 patients treated with cladribine between March 2021 and January 2024. The diagnosis of VAMS was confirmed in 51 patients, PPMS in 4 patients, and SPMS with exacerbations was diagnosed in 7 cases. Of these, 3 patients completely completed therapy more than a year ago, 20 people received 2 courses of the drug less than a year ago, 39 patients underwent 1 course of therapy. The effect of cladribine on reducing disease activity and progression, as well as the safety of therapy, was evaluated. After 1 course, the number of patients with activity decreased by 66.4%, after 2 years of therapy - by 72.7%. The mean annual frequency of exacerbations decreased from 1.32 to 0.2 after 12 months, and to 0.086 exacerbations per year after 24 months. The level of disability assessed by the EDSS scale remained virtually unchanged throughout the follow-up. The most common adverse events were haematological abnormalities in the form of lymphopenia and leukopenia. Most patients had mild grade 1-2 lymphopenia on the toxicity scale and recovered to the recommended values (>0.8·109/l) by the beginning of the second course of therapy. No cases of serious adverse events were reported. The results obtained indicate the high efficacy and favorable safety profile of cladribine and are consistent with the data of clinical trials of the drug.

Частота развития и характер течения постковидного синдрома у пациентов с ревматоидным артритом и спондилоартритами

The purpose — to conduct a comparative analysis of the course of post-COVID syndrome in patients with rheumatoid arthritis and spondyloarthritis. Material and methods. The study included 140 patients: 91 patients (65%) with rheumatoid arthritis (RA) and 49 (35%) with spondyloarthritis (SpА). The presence of post-COVID syndrome, RA and SpA activity were assessed and risk factors for exacerbations of major diseases were identified 3, 6, 9, 12 months after COVID-19. Results. The incidence of post-COVID syndrome among patients with RA was 73.7%, among patients with SрA — 61.3%. Most often, patients with RA and SpA reported fatigue, and/or muscle pain, and/or headaches, and/or dysautonomia, and/or cognitive impairment 87.3% and 71%, respectively, increased joint pain — the second most common complaint — 81.6% and 65.1%, respectively. Patients with RA had more frequent and longer complaints characteristic of post-COVID syndrome compared to patients with SpA. The maximum value of activity in RA, AS, and PsA was revealed 3 months after COVID-19. Among patients with RA, the main factors influencing the frequency of exacerbations after 3 months were cardiovascular diseases, female gender, viral lung damage, RA activity before NCI, COVID-19 symptoms; among patients with PsA: exacerbation of PsA before COVID-19, initial glucocorticosteroid therapy, COVID-19 symptoms; among patients with AS: symptoms of COVID-19. Conclusions. Among patients with RA, regardless of the severity of COVID-19, post-COVID syndrome was more common compared with patients with SpA. The largest number of patients in exacerbation was recorded 3 months after the COVID-19. The largest number of risk factors for exacerbations at 3 months after COVID-19 was recorded among patients with RA and PsA; among patients with AS, only the symptoms of COVID-19 were affected.

The Impact of Bronchiectasis on the Clinical Characteristics of Non-Severe Asthma.

Current literature primarily delves into the relationship between bronchiectasis and severe asthma, and only a few studies have evaluated the impact of bronchiectasis in patients with non-severe asthma. Therefore, this study investigated the clinical impact of bronchiectasis in patients with non-severe asthma. A prospective observational study of 140 non-severe asthmatic patients with (bronchiectasis group) and without bronchiectasis (control group) was conducted between September 2012 and February 2022. The bronchiectasis and control groups were compared in terms of demographics, lung function, asthma control test (ACT) results, exacerbation history, and respiratory medications. Among 140 non-severe asthmatic subjects, approximately 15.7% (n = 22) had bronchiectasis. The most common type of bronchiectasis was cylindrical type (90.7%). The left lingular division was the most frequently involved lung lobe (20.4%). There were no significant differences in the demographics (age, sex, body mass index, smoking history, and comorbidities) or ACT results between the 2 groups. The bronchiectasis group used inhaled corticosteroids/long-acting β2-agonists (P = 0.074) and mucolytics (P < 0.001) more frequently than the control group. Compared to the control group, the bronchiectasis group had lower forced expiratory volume in 1 second (FEV1) (L) (1.9 ± 0.7 L vs. 2.3 ± 0.9 L, P = 0.039) and FEV1%predicted (67.2 ± 22.2%predicted vs. 77.1 ± 20.0%predicted, P = 0.038). The rate of hospital admission to a general ward in the preceding year was significantly higher in the bronchiectasis group compared to those of the control group (23.8% vs. 3.5%, P = 0.005) with an adjusted odds ratio of 6.308 (95% confidence interval, 1.401-28.392). Patients with non-severe asthma and bronchiectasis had lower lung function and more frequent exacerbations requiring hospitalization than those without bronchiectasis. More attention is needed for asthmatic patients with bronchiectasis, even if the asthma is not severe.

Clinical, therapeutic and pathophysiological aspects of Darier's disease

Darier Disease is a rare autosomal dominant inherited skin disorder classified as an acantholytic dermatosis. It manifests around puberty as brownish keratotic papules of skin folds and seborrheic areas, associated with onychopathy and mucosal involvementand have a chronic relapsing-remitting course with frequent exacerbations triggered by sun exposure, heat, friction, or infections. Darier patients have an increased risk of neuropsychiatric disorders, type 1 diabetes and heart failure. Short-term management relies on antibiotics/antiviral, topical corticosteroids and/or retinoids. Moisturizers, sun protection and avoiding triggers are essential for long-term management. Conventional long-term treatment is not standardized and many topical treatments, physical and surgical measures and systemic treatments are described in the literature.

Bronchiectasis-COPD Overlap Syndrome (BCOS) among the Nepalese Patients: Emerging disease from a developing country

Background and objective: There is no clearly specified diagnostic criteria to identify BCOS in Nepalese context. So this first, observational cross-sectional study was conducted to determine the current situation, main clinical practices, and features of BCOS in Nepalese patients, exploring its clinical trajectory and severity. Methods: This is a hospital based descriptive cross-sectional study conducted, where patients presenting with respiratory symptoms complex were subsequently enrolled by purposive sampling. Descriptive Statistics was calculated using Absolute and Relative Frequencies for categorical variables and mean and standard deviation for numerical ones. P-value of &lt;0.05 was considered significant. Results: Out of 236 patients of Respiratory Symptoms Complex, prevalence of BCOS was 22.03%. 57.7% were males with mean age of 67.8 years. Among BCOS cohorts, 92.3% were smokers and 73 % had significant exposure to indoor air pollution. 63.5% of the patients had past history of tuberculosis and cardio-metabolic co-morbidities were seen in 34.6% of the patients. The most frequent symptoms were cough and shortness of breath and the commonest sign was bilateral basal coarse crackles. Frequent exacerbations were present in 25% of the patients and PFT revealed obstructive pattern in 71% of the BCOS patients with a mean FACED score of 3.94±1.62. Conclusion: Among the patients presenting with Respiratory symptom complex in Nepal, BCOS is common and is more prevalent in elderly male, having a high co-morbidities, usually following a course of slowly progressive breathlessness, with higher incidence of exacerbation and poorer functional outcome.

Clinical manifestations and prognosis of giant cell arteritis: A retrospective cohort study

The aim of the study was to evaluate the clinical manifestations and survival of patients with giant cell arteritis (GCA).Methods. A retrospective study included 166 patients with newly diagnosed GCA. Clinical, laboratory and instrumental data, three sets of classification criteria were used to confirm the diagnosis: the American College of Rheumatology (ACR) 1990, the revised ACR criteria of 2016 and/or the new ACR and European Alliance of Associations for Rheumatology (EULAR) 2022 criteria. Some of the patients underwent instrumental investigations: temporal artery ultrasound Doppler (n=61), contrast-enhanced computed tomography (CT) (n=5), CT angiography (n=6), magnetic resonance imaging (n=4), magnetic resonance angiography (n=3) and 18F-FDG positron emission tomography/CT (n=47). Overall and recurrence-free survival were analyzed using survival tables, Kaplan – Meier method.Results. The most frequent first manifestations of GCA were headache (81.8%), weakness (64%), fever (63.8%) and symptoms of rheumatic polymyalgia (56.6%). Changes of temporal arteries in color duplex scanning were detected in 44 out of 61 patients. GCs therapy was performed in all patients who agreed to be treated (n=158), methotrexate was used in 49 out of 158 patients, leflunomide – in 9 patients. In 45 (28.5%) out of 158 patients a stable remission was achieved as a result of GCs monotherapy, in 120 (75.9%) patients long-term maintenance therapy with GCs was required to prevent exacerbations, including 71 (44.9%) patients – in combination with methotrexate or other immunosuppressive drugs. The follow-up period of patients with a history of relapses was 21.0 (8.0–54.0) months. Relapses developed in 73 (46.2%) patients. The overall one-year survival rate was 97.1% [95% confidence interval (CI): 94.3; 99.9], and the five-year survival rate of patients was 94.6% [95% CI: 90.2; 99.0]. The one-year relapse-free survival rate was 86.4% [95% CI: 80.5; 92.3], and the five-year relapse-free survival rate was 52.4% [95% CI: 42.0; 62.8]. 12 (7.2%) of 166 patients died. The cause of death was myocardial infarction in two patients, stroke in two patients, and breast cancer in one patient; in the remaining seven cases, the cause of death was not determined.Conclusion. Given the high frequency of disease exacerbation, patients with GCA require long-term follow-up, especially during the first year after diagnosis.

Clinical And Genetic Risk Factors For Asthma Exacerbations And Mortality In Adults

Background — According to epidemiological studies, nearly 7 million people in Russia suffer from bronchial asthma (BA), of which 1 million have a severe form of the disease that is difficult to control. Insufficiently effective control of BA leads to a reduction in the quality of life, the development of its more severe forms, an increase in the frequency of exacerbations of the disease, and an increase in the number of disability and death cases in patients. Objective — The goal of our research was conducting a long-term cohort study of BA in adults living in the Republic of Bashkortostan and assessing the clinical and prognostic value of internal and external risk factors for exacerbation and death from BA. Methods and Results — We analyzed the medical records of 213 BA patients 18 to 67 years а age from 2012 through 2022. Genotyping of six SNPs in ADRB2 (rs1042713, rs1042714), CRHR1 (rs242939, rs1876828), NR3C1 (rs41423247), and HRH3 (rs3787429) genes was performed by real-time polymerase chain reaction. Using regression analysis, we assessed predictors of the risks of exacerbation and death in BA and built multivariate models for each outcome. Conclusion — As a result of regression analysis, significant clinical and prognostic risk factors for re-exacerbation and death from BA were identified.

Contralateral knee pain exacerbation after total knee arthroplasty and its impact on functional activity.

The purposes of the present study were to (1) describe the prevalence of contralateral knee pain exacerbation after total knee arthroplasty (TKA), (2) explore the risk factors for pain exacerbation, and (3) verify the association of contralateral knee pain with future functional activity. We consecutively recruited outpatients with osteoarthritis of both knees who had primary TKA planned. The contralateral knee pain using a Numerical Rating Scale (NRS) and the functional activities subdomain of the new Knee Society Knee Scoring System (KSS) were assessed preoperatively and at 1, 3, and 6months postoperatively. Among patients with < 5 NRS points preoperatively, we described the frequency of the contralateral knee pain exacerbation, defined as a ≥ 2-point increase from preoperative pain at each postoperative visit. An exploratory analysis was performed to identify preoperative risk factors for contralateral knee pain exacerbation. A linear mixed model was fit to examine the association of the contralateral knee pain with KSS functional activities at subsequent visits. Among 315 patients, 14.6%, 24.1%, and 27.6% of patients experienced contralateral knee pain exacerbation at 1, 3, and 6months postoperatively, respectively. The identified preoperative risk factors were low quadriceps strength and higher Kellgren-Lawrence grade on the non-operative knee, along with severe pain on the operative knee. The magnitude of the association between contralateral knee pain and worsening KSS functional activities increased with subsequent visits (p for interaction < 0.001). The frequency and impact of pain exacerbation on the contralateral knee increase after TKA and should be carefully evaluated for a prolonged period of time.

The Comorbidity of Patient-Reported Crohn's Disease Activity and Depression: The Role of Health Behavior Mediators.

Longitudinal research reveals a unidirectional relationship between a nonsomatic symptom of depression, a negative view of the self, and later reported Crohn's disease (CD) activity. We evaluated whether health behaviors mediated this association using a longitudinal design. We studied 3304 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, a symptom-specific index of depression, and measures of physical activity, smoking, and sleep quality. Crohn's disease status and the cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We specified single-mediator and multiple-mediator models to elucidate the depression-disease activity relationship. Among 2395 females and 909 males, we found a significant mediation effect for activity level (P < .001) after adjusting for age, sex, and body mass index. There was no evidence that sleep quality and smoking are significant single mediators. When we considered multiple mediation models, smoking and less activity partially mediate the depression-CD association. Smoking and lower levels of physical activity are potential mediators of the unidirectional association between a nonsomatic symptom of depression-a negative view of the self-and patient-reported CD activity. Evaluating and treating specific symptoms of depression may reduce the frequency of CD exacerbations.

Diminished airway host innate response in people with cystic fibrosis who experience frequent pulmonary exacerbations.

Pulmonary exacerbations are clinically impactful events that accelerate cystic fibrosis (CF) lung disease progression. The pathophysiological mechanisms underlying an increased frequency of pulmonary exacerbations have not been explored. To compare host immune response during intravenous antibiotic treatment of pulmonary exacerbations in people with CF who have a history of frequent versus infrequent exacerbations. Adults with CF were recruited at onset of antibiotic treatment of a pulmonary exacerbation and were categorised as infrequent or frequent exacerbators based on their pulmonary exacerbation frequency in the previous 12 months. Clinical parameters, sputum bacterial load and sputum inflammatory markers were measured on day 0, day 5 and at the end of treatment. Shotgun proteomic analysis was performed on sputum using liquid chromatography-mass spectrometry. Many sputum proteins were differentially enriched between infrequent and frequent exacerbators (day 0 n=23 and day 5 n=31). The majority of these proteins had a higher abundance in infrequent exacerbators and were secreted innate host defence proteins with antimicrobial, antiprotease and immunomodulatory functions. Several differentially enriched proteins were validated using ELISA and Western blot including secretory leukocyte protease inhibitor (SLPI), lipocalin-1 and cystatin SA. Sputum from frequent exacerbators demonstrated potent ability to cleave exogenous recombinant SLPI in a neutrophil elastase dependent manner. Frequent exacerbators had increased sputum inflammatory markers (interleukin (IL)-1β and IL-8) and total bacterial load compared to infrequent exacerbators. A diminished innate host protein defence may play a role in the pathophysiological mechanisms of frequent CF pulmonary exacerbations. Frequent exacerbators may benefit from therapies targeting this dysregulated host immune response.

Clinical and bronchial parameters associated with the exacerbation frequency of severe preschool wheezers

Clinical and bronchial parameters associated with the exacerbation frequency of severe preschool wheezers

Unmasking the Silent Threat: Periodontal Health's Impact on COPD Severity and Hospitalization.

This study investigated the relationship between chronic obstructive pulmonary disease (COPD) and periodontitis, focusing on how periodontal health impacts COPD airflow limitation, exacerbations, and hospitalization. Periodontitis, a multifactorial inflammatory disease, is characterized by destruction of tooth-supporting structures, while COPD is a global pulmonary disorder with high mortality. A total of 199 COPD patients aged over 40 years underwent lung function tests (spirometry), 6 min walk test, and St George's Respiratory Questionnaire-COPD (SGRQ-C) to assess lung health. Periodontal indices such as probing depth (PD), clinical attachment loss (CAL), and plaque index (PI) were assessed. We found a significant negative correlation between periodontal disease severity and lung function (lower FEV1, FVC, and FEV1/FVC ratio) after adjusting for smoking. Likewise, periodontal parameters (PPD, PI, and CAL) exhibited negative correlations with lung function. These periodontal indices were independently associated with airflow limitation severity, exacerbations frequency, and prior-year hospitalization. Linear regression indicated that each unit increase in PPD, PI, and CAL corresponded to estimated increases in GOLD airflow limitation grading (0.288, 0.718, and 0.193, respectively) and number of exacerbations (0.115, 0.041, and 0.109, respectively). In logistic regression, PPD, PI, and CAL adjusted odds ratios (ORs) were estimated to increase by 1.29 (95%CI: 1.03-1.62), 3.04 (95%CI: 1.28-7.2), and 1.26 (95%CI: 1.06-1.49), respectively, for hospitalization in previous year. Periodontitis is associated with COPD airflow limitation, exacerbation, and hospitalization, with PI being the most clinically relevant periodontal factor. Dentists and physicians should monitor and increase awareness among COPD patients to maintain oral hygiene for prevention of periodontal diseases and mitigate its effect on COPD progression.