Severity Of Respiratory Symptoms Research Articles

Process of Reliability of the Ventilatory Workload Kinetic Index and Prioritization in the Intrahospital Clinical Setting

Background and Objectives: The Ventilatory Workload Kinetic Index (VWKI) has been proposed as a clinical instrument to evaluate ventilatory balance–imbalance. However, the regulated application of scales that allow an integral evaluation of the object of study and their subsequent reliability evaluation should be continuous. The objective was to determine the reliability of the VWKI between two evaluators and its applicability in the clinical field of physiotherapy. Materials and Methods: The methodology was divided into three stages: (i) induction period, (ii) application of the VWKI, and (iii) assessment of reliability. Results: The VWKI total score obtained excellent inter-rater reliability (ICC = 0.913, p < 0.05). The airway resistance (AR) showed moderate inter-rater reliability (ICC = 0.528, p < 0.05), while the use of accessory musculature (UAM) showed poor inter-rater reliability (ICC = 0.483, p < 0.05). In the physiotherapy care prioritization system, for both evaluator A (EA) and evaluator B (EB), the total VWKI score was significantly higher in priority 1 (p = 0.001; p < 0.05, respectively). Regarding the total VWKI score by services, it was observed that both EA and EB rated the VWKI significantly higher in the intensive care unit (ICU) than in medicine and the other services (p = 0.001, p = 0.0001 and p < 0.05, p < 0.05, respectively). Conclusions: VWKI is highly reliable in the total score. It is also consistent with the system of prioritization of physiotherapy care and the ability to determine the severity of clinical respiratory symptoms.

Real-World and Patient-Reported Outcomes of Dupilumab and Other Biological Drugs for Chronic Obstructive Pulmonary Disease—A Systematic Review

Background: Over the last few decades, the efficacy of biological therapies for COPD has been evaluated by different randomized controlled trials (RCTs). Still, the evaluation of real-world data and patient-reported outcome measures (PROMs) have not been performed in this field before. In the current work, we present a systematic literature review of the real-world data and PROMs of biological treatments for COPD. Methods: Three large databases (MEDLINE/PubMed, Scopus, and ScienceDirect) were utilized for the systematic literature review. Clinical studies (RCT, cohorts, case series/reports) assessing patients with COPD treated by any biological therapy were included. Results: The review resulted in twelve eligible studies (nine randomized controlled trials and three “real-world” case series/reports). The evaluation of PROMs in the included studies was mainly limited to the severity and burden of respiratory symptoms. Most biological therapies were associated with improved PROMs compared to the baseline, although not for the placebo. Dupilumab was the only biologic therapy with proven efficacy in RCT for both objective and subjective measures. One prior study reported patients’ self-perceived drug effects, and none evaluated patients’ perceived disease status. Only 25 patients were assessed in a real-world setting for all biologic therapies combined. Real-world data were retrospective in the form of case reports or series. Conclusions: There are limited data on patients’ experience with biological therapies for COPD. While real-world data and PROMs are missing, biases such as a placebo effect must be considered, requiring their incorporation with objective outcomes from prospective controlled trials.

Peculiarities of granulocyte-macrophage and macrophage colony-stimulating factors receptors expression in subpopulations of peripheral blood monocytes of patients with chronic obstructive pulmonary disease

Introduction. To analyze of the severity of respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD), depending on the presence of an exacerbation or novel coronavirus infection (NCVI), taking into account the activity of acute phase blood parameters.Materials and methods. The medical documentation of 162 patients with COPD was studied, which were divided into 3 groups: group 1 (n=61) ‒ COPD and NCVI, group 2 (n=53) – stable COPD, group 3 (n=48) ‒ COPD exacerbation. The severity of respiratory symptoms was assessed using points. To assess the activity of inflammation the following biochemical indicators were used ‒ C-reactive protein (CRP) and fibrinogen (g/L).Results. According to the severity of cough and the intensity of dyspnea on the mMRC scale, the first, second and third groups did not differ statistically (p=0.07). Patients of the first group (82.5%) characterized by the absence of classical criteria for exacerbation of COPD. In terms of the severity of sputum production, the first, second and third groups are statistically different (p=0.0001). The first, second and third groups differ significantly in the level of serum CRP (p=0.0001) and fibrinogen (p=0.009). According to the results of the correlation analysis, some relationships found between respiratory symptoms and the level of CRP and fibrinogen.Conclusion. The clinical feature of the associated course of stable COPD and NCVI is the presence of severe dyspnea and the absence of classic criteria for exacerbation of COPD. Systemic inflammation in NCVI and stable COPD are more pronounced than in isolated stable COPD or exacerbation and correlates with cough and dyspnea. Practitioners for the differential diagnosis of NCVI in stable COPD can use the data obtained.

The validity of single-item measures of health-related quality of life across groups differing in acute respiratory symptom severity

PurposePractical considerations precluding health-related quality of life (HRQOL) monitoring in population and clinical research have spawned development of improved items for more brief surveys of frequently measured HRQOL outcomes. The aim of this study was to validate the use of the Quality of Life General (QGEN-8), a shorter 8-item alternative to the longer 36-item short form (SF)-36 Health Survey for measuring the same eight HRQOL domains across groups of adults with varying severity of acute respiratory symptoms, such as cough and sore throat.MethodsNational Opinion Research Center (NORC) representative probability (N = 1,648) and supplemental opt-in (N = 5,915) U.S. adult samples were surveyed cross-sectionally online in 2020. Parallel analyses compared QGEN-8 and SF-36 estimates of group means for each of eight matching profile domains and summary physical and mental scores across groups differing in severity of acute symptoms and chronic respiratory conditions using analysis of covariance (ANCOVAs) controlling for socio-demographics and presence of chronic respiratory conditions.ResultsIn support of discriminant validity, ANCOVA estimates of QGEN-8 means with SF-36 estimates revealed the same patterns of declining HRQOL with the presence and increasing severity of symptoms and chronic condition severity.ConclusionQGEN-8® shows satisfactory validity and warrants further testing in cross-sectional and longitudinal population and clinical survey research as a more practical method for estimating group differences in SF-36 profile and summary component HRQOL scores.

The Impact of Malnutrition on Chronic Obstructive Pulmonary Disease (COPD) Outcomes: The Predictive Value of the Mini Nutritional Assessment (MNA) versus Acute Exacerbations in Patients with Highly Complex COPD and Its Clinical and Prognostic Implications.

Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. This was a prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had a normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear regression models showed that the MNA score was associated with dyspnea and respiratory symptom severity, assessed by the Modified British Medical Research Council (mMRC) scale and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1, and with poorer QoL, as assessed by the EQ-5D-3 questionnaire. Competing risk analysis according to nutritional status based on the MNA Total Score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with sub-hazard ratios of 3.08 (1.40-6.80), p = 0.015, and 4.64 (1.71-12.55), p = 0.0002, respectively. Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

New medical technologies in cough therapy: results of a double-blind randomized placebo-controlled multicenter clinical trial

To study the efficacy and safety of Eladis® in comparison with placebo in patients with non-productive cough. A phase III clinical trial enrolled 250 patients aged 18-65 years with acute respiratory viral infection with upper respiratory tract involvement or acute bronchitis. Patients were randomized into 2 groups of 125 subjects: group 1 received Eladis® (40 mg tablets), group 2 received a matching placebo. The patients received the study drugs 1 tablet BID for 7-14 days. After the treatment, patients were followed up (day 7±2) to assess the effect of therapy on the frequency of coughing attacks, the frequency and severity of daytime and nocturnal cough, the severity of cough, the duration of clinical cough cure, and the effect on the severity of the main acute respiratory viral infection symptoms. The results of the study demonstrate the overall efficacy and statistically significant superiority of Eladis® over placebo: there were significant differences between the study groups in the proportion of patients who decreased the coughing attack frequency by ≥50% by day 5 (p<0.0001). In addition, the clinical cure of cough in the Eladis® group occurred 2 days earlier: the median time was 6 days, vs 8 days in placebo group. There was a decrease in the frequency of cough attacks and a decrease in its severity by more than 3.5 points by day 5 of treatment. All the effects were associated with high safety of the drug.

Efficacy and Safety of Platelet-Rich Plasma on Bronchopleural Fistula: A Pilot Prospective Cohort Study

IntroductionBronchopleural fistula (BPF) is associated with high morbidity and mortality rates in patients undergoing pulmonary resections. Surgery, bronchoscopy, and conservative management have their limitations for small fistulas. Platelet-rich plasma (PRP) has regenerative properties, which might be efficient in enhancing tissue recovery and repairing small BPF. This study aimed to investigate efficacy and safety of PRP on BPF. MethodsThis is a pilot prospective cohort study. Patients whose fistulas smaller than 4mm were enrolled in this study, treated with PRP under bronchoscopy and followed up at 2 weeks and 4–6 weeks after the last PRP treatment. The cure rate, improvement rate and ineffectiveness rate were investigated. The severity of respiratory symptoms was evaluated by modified Medical Research Council dyspnea scale (mMRC) and COPD Assessment Test (CAT). The recurrence of fistula, new infection and mortality rate were examined. Adverse events were documented to explore the safety profile of PRP therapy. ResultsA total of 16 patients (mean age, 50.1 years) met the eligibility criteria. The median time from the first PRP treatment to the closure of the fistula was 12.0 (IQR 6.0, 21.5) days. Our findings indicate an effectiveness rate of 87.6%, with 68.8% of cure and 18.8% of improvement, along with significant improvement of respiratory symptoms evaluated by mMRC (P<0.001) and CAT (P<0.001). No recurrent of fistulas, newly developed infection, or death was observed. Adverse events of the procedure were most mild (82.6%) and temporary. ConclusionsPRP is a potential treatment for small BPF and is well tolerated.

Echinacea purpurea: An overview of mechanism, efficacy, and safety in pediatric upper respiratory infections and otitis media

Pediatric upper respiratory infections (URIs) and otitis media (OM) significantly impact the health of children globally. Echinacea purpurea, known for its immunomodulatory, anti-inflammatory, and antimicrobial properties, has been historically used to treat various ailments, suggesting its potential as an adjunctive treatment in pediatric respiratory conditions. This narrative review synthesizes literature from January 2000 to December 2023 on the efficacy and safety of E. purpurea in treating pediatric URIs, including OM. It focuses on clinical trials and empirical studies that explore the mechanisms of action, such as the modulation of cytokine production, inhibition of NF-κB signaling, and antimicrobial effects. The analysis reveals mixed outcomes regarding the efficacy of E. purpurea in pediatric populations, attributed partly to variability in study designs and lack of standardized treatment protocols. While some studies report reduced severity and duration of respiratory symptoms, others indicate minimal or no significant difference compared to placebo. The review also highlights the need for specifically designed products that cater to the unique physiological and metabolic needs of children. Rigorous, well-designed clinical trials are crucial for establishing clear guidelines on the use of E. purpurea in pediatric respiratory care, ensuring its safe and effective application in improving health outcomes for children.

Interactions between Cognitive, Affective, and Respiratory Profiles in Chronic Respiratory Disorders: A Cluster Analysis Approach.

This study conducted at Leamna Pulmonology Hospital investigated the interrelations among cognitive, affective, and respiratory variables within a cohort of 100 patients diagnosed with chronic respiratory conditions, utilizing sophisticated machine learning-based clustering techniques. Spanning from October 2022 to February 2023, hospitalized individuals confirmed to have asthma or COPD underwent extensive evaluations using standardized instruments such as the mMRC scale, the CAT test, and spirometry. Complementary cognitive and affective assessments were performed employing the MMSE, MoCA, and the Hamilton Anxiety and Depression Scale, furnishing a holistic view of patient health statuses. The analysis delineated three distinct clusters: Moderate Cognitive Respiratory, Severe Cognitive Respiratory, and Stable Cognitive Respiratory, each characterized by unique profiles that underscore the necessity for tailored therapeutic strategies. These clusters exhibited significant correlations between the severity of respiratory symptoms and their effects on cognitive and affective conditions. The results highlight the benefits of an integrated treatment approach for COPD and asthma, which is personalized based on the intricate patterns identified through clustering. Such a strategy promises to enhance the management of these diseases, potentially elevating the quality of life and everyday functionality of the patients. These findings advocate for treatment customization according to the specific interplays among cognitive, affective, and respiratory dimensions, presenting substantial prospects for clinical advancement and pioneering new avenues for research in the domain of chronic respiratory disease management.

The Recipe for Cure or Disaster?

Abstract Drug-induced pulmonary toxicity is a rare adversity that occurs to a small minority of individuals on exposure to an agent. It may affect the alveoli, upper and lower airways, pleura, pulmonary vasculature, muscles of respiration, and the central nervous system governing respiratory controls. Here is a case about solving the mystery behind increased severity of respiratory symptoms in a known case of non-Hodgkin’s lymphoma on maintenance chemotherapy post complete response, and finding the agent of chaos.

FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study

Interstitial lung disease (ILD) is a common manifestation of idiopathic inflammatory myopathies (IIM) and a substantial contributor to hospitalisation, increased morbidity, and mortality. In-vivo evidence of ongoing tissue remodelling in IIM-ILD is scarce. We aimed to evaluate fibroblast activation in lungs of IIM-patients and control individuals using ⁶⁸Ga-labelled inhibitor of Fibroblast-Activation-Protein (FAPi) based positronic emission tomography and computed tomography imaging (PET/CT). In this prospective observational pilot study, consecutive patients with IIM and participants without rheumatic conditions or ILD serving as a control group were recruited at the Medical University of Vienna, Austria, and underwent FAPi PET/CT imaging. Standard-of-care procedures including clinical examination, assessment of severity of dyspnoea, high-resolution computed tomography (HR-CT), and pulmonary function testing (PFT) were performed on all patients with IIM at baseline and for patients with IIM-ILD at follow-up of 12 months. Baseline pulmonary FAPi-uptake was assessed by the maximum (SUVmax) and mean (SUVmean) standardized uptake values (SUV) over the whole lung (wl). SUV was corrected for blood pool background activity and target-to-background ratios (TBR) were calculated. We compared pulmonary FAPi-uptake between patients with IIM-ILD and those without ILD, as well as controls, and correlated baseline FAP-uptake with standard diagnostic tools such as HR-CT and PFT. For predictive implications, we investigated whether patients with IIM and progressive ILD exhibited higher baseline FAPi-uptake compared to those with stable ILD. Metrics are reported as mean with standard deviation (±SD). Between November 16, 2021 and October 10, 2022, a total of 32 patients were enrolled in the study. Three participants from the control group were excluded due to cardiopulmonary disease. In individuals with IIM-ILD (n=14), wlTBRmax and wlTBRmean were significantly increased as compared with both non-ILD-IIM patients (n=5) and the control group (n=16): wlTBRmax: 2.06±1.04 vs. 1.04±0.22 (p=0.019) and 1.08±0.19 (p=0.0012) and wlTBRmean: 0.45±0.19 vs. 0.26±0.06 (p=0.025) and 0.27±0.07 (p=0.0024). Similar values were observed in wlTBRmax or wlTBRmean between non-ILD IIM patients and the control group. Patients with progressive ILD displayed significantly enhanced wlTBRmax and wlTBRmean values at baseline compared to patients with stable ILD: wlTBRmax: 1.30±0.31 vs. 2.63±1.04 (p=0.0084) and wlTBRmean: 0.32±0.08 vs. 0.55±0.19 (p=0.021). Strong correlations were found between FAPi-uptake and disease extent on HR-CT (wlTBRmax: R=0.42, p=0.07; wlTBRmean: R=0.56, p=0.013) and severity of respiratory symptoms determined by the New York Heart Association (NYHA) classification tool (wlTBRmax: R=0.52, p=0.022; wlTBRmean: R=0.59, p=0.0073). Further, pulmonary FAPi-uptake showed inverse correlation with forced vital capacity (FVC) (wlTBRmax: R=-0.56, p=0.012; wlTBRmean: R=-0.64, p=0.0033) and diffusing capacity of the lungs for carbon monoxide (DLCO) (wlTBRmax: R=-0.52, p=0.028; wlTBRmean: R=-0.68, p=0.0017). Our study demonstrates higher fibroblast activation in patients with IIM-ILD compared to non-ILD patients and controls. Intensity of pulmonary FAPi accumulation was associated with progression of ILD. Considering that this study was carried out on a small population, FAPi PET/CT may serve as a useful non-invasive tool for risk stratification of lung disease in IIM. The Austrian Research Fund.

The impact of daily supplementation with rhamnogalacturonan-I on the gut microbiota in healthy adults: A randomized controlled trial

Pectin and its derivatives have been shown to modulate immune signaling as well as gut microbiota in preclinical studies, which may constitute the mechanisms by which supplementation of specific pectic polysaccharides confers protection against viral respiratory infections. In a double-blind, placebo-controlled rhinovirus (RV16) challenge study, healthy volunteers were randomized to consume placebo (0.0 g/day) (N = 46), low-dose (0.3 g/day) (N = 49) or high-dose (1.5 g/day) (N = 51) of carrot derived rhamnogalacturonan-I (cRG-I) for eight weeks and they were subsequently challenged with RV-16. Here, the effect of 8-week cRG-I supplementation on the gut microbiota was studied. While the overall gut microbiota composition in the population was generally unaltered by this very low dose of fibre, the relative abundance of Bifidobacterium spp. (mainly B. adolescentis and B. longum) was significantly increased by both doses of cRG-1. Moreover, daily supplementation of cRG-I led to a dose-dependent reduction in inter- and intra-individual microbiota heterogeneity, suggesting a stabilizing effect on the gut microbiota. The severity of respiratory symptoms did not directly correlate with the cRG-I-induced microbial changes, but several dominant groups of the Ruminococcaceae family and microbiota richness were positively associated with a reduced and hence desired post-infection response. Thus, the present results on the modulation of the gut microbiota composition support the previously demonstrated immunomodulatory and protective effect of cRG-I during a common cold infection.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE: RATE OF THERAPIOTIC ADHERENCE IN OUTPATIENT PRACTICE

The adherence of a patient with chronic obstructive pulmonary disease (COPD) to treatment is of utmost importance as it prevents the disease progression and the delayed complication development that determine the quality of life and life span.&#x0D; The purpose of the study is to assess the level of adherence for patients with COPD to drug therapy with respiratory drugs, to identify factors influencing the adherence, and study 5-year survival rate based on adherence level.&#x0D; Materials and Methods. The study enrolled 150 patients with COPD (87 men, and 63 women, mean age 58.3±0.86 years). Pulmonary function (FEV1, FVC, FEV1/FVC), severity of respiratory symptoms (mMRS scale, CAT questionnaire), and disease severity were assessed (GOLD, 2022). Adherence to COPD treatment was determined according to the Morisky-Green test (1986). Five-year survival rate of patients was analyzed.&#x0D; Results. Low adherence to treatment in patients with COPD was revealed: 1 month after the initiation or correction of respiratory therapy, only 32 patients (21.3 %) were assessed as adherent, 56 patients (37.3 %) were insufficiently adherent, and 62 patients (41.3 %) were non-adherent to treatment. Adherence to treatment was associated with age, disease severity, severity of respiratory symptoms, FEV1 and did not depend on gender. In five years, survival rate in the group of non-adherent patients (89.5 %) and insufficiently adherent patients (80.4 %) was significantly higher than in the group of adherent one (61.9 %). It is associated with a more severe status of patients who are adherent to therapy.&#x0D; Conclusion. The authors identified an insufficient adherence level in patients with COPD. Elderly patients with a more severe course of the disease, low FEV1 levels, and severe exacerbations are more adherent to respiratory drug therapy. Worse five-year survival rates were observed in the group of patients who were adherent to therapy. It was associated with more severe clinical status, age and comorbidity.

SunGold Kiwifruit Consumption Restores Adequate to Optimal Vitamin C Status in People with a History of Severe Respiratory Infections.

Severe respiratory infections are characterised by depleted vitamin C and elevated inflammation and oxidative stress. The aim of this study was to recruit people with a history of severe respiratory infections to undergo a six-week intervention with SunGold kiwifruit to determine if this could restore adequate vitamin C status. Secondary outcomes included changes in inflammatory and oxidative stress biomarkers, self-reported fatigue and subjective mood, and the incidence, duration and severity of respiratory symptoms. The total cohort comprised 20 adults (65% female, age range 31-84 years). The participants had a low median fruit and vegetable intake of 2.3 servings/day and a correspondingly low vitamin C intake of 46 mg/day. Circulating vitamin C status was a median of 45 µmol/L and was in the hypovitaminosis range in 25% of the cohort. Following intervention with two SunGold kiwifruit/day (equivalent to ~300 mg vitamin C), there was an increase in plasma vitamin C concentrations to >60 µmol/L (p < 0.05). Approximately 20% of the participants were unable to reach adequate vitamin C status (≥50 µmol/L), possibly due to current smoking, which enhances vitamin C turnover, and a strong inverse correlation between body weight and vitamin C status (r = -0.734, p < 0.05). Following the intervention, there were indications towards decreases in the inflammatory biomarkers C-reactive protein and TNFα (p > 0.05), but no changes in oxidative stress biomarkers (F2isoprostanes, protein carbonyls). There were decreases in fatigue and depression (p < 0.05) and a lower number of individual respiratory symptoms reported during the kiwifruit intervention phase (8.5 vs. 10, p = 0.05). Overall, the consumption of two SunGold kiwifruit per day for six weeks was able to restore adequate to saturating vitamin C status in ~80% of the participants. Smokers and people with higher body weight may need larger doses and/or longer duration of supplementation. The contribution of vitamin C to reducing fatigue, depression, and number of respiratory symptoms warrants further investigation.

Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial

Addition of macrolide antibiotics to β-lactam antibiotics for the treatment of patients in hospital with community-acquired pneumonia is based on results from observational studies and meta-analyses rather than randomised clinical trials. We investigated if addition of the macrolide clarithromycin to treatment with a β-lactam antibiotic in this population could improve early clinical response-the new regulatory endpoint for community-acquired pneumonia-and explored the possible contribution of modulation of the inflammatory host response to that outcome. The ACCESS trial was a phase 3 prospective, double-blind, randomised controlled trial, in which adults in hospital with community-acquired pneumonia who had systemic inflammatory response syndrome, Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin 0·25 ng/mL or more were enrolled in 18 internal medicine departments of public Greek hospitals. Patients were randomly assigned (1:1) by computer-generated block randomisation to standard of care medication (including intravenous administration of a third-generation cephalosporin or intravenous administration of β-lactam plus β-lactamase inhibitor combination) plus either oral placebo or oral clarithromycin 500 mg twice daily for 7 days. Investigators, staff, and patients were masked to group allocation. The primary composite endpoint required that patients fulfilled both of the following conditions after 72 hours (ie, day 4 of treatment): (1) decrease in respiratory symptom severity score of 50% or more as an indicator of early clinical response and (2) decrease in SOFA score of at least 30% or favourable procalcitonin kinetics (defined as ≥80% decrease from baseline or procalcitonin <0·25 ng/mL), or both, as an indicator of early inflammatory response. Participants who were randomly assigned and received allocated treatment were included in the primary analysis population. This trial is complete and is registered with the EU Clinical Trials Register (2020-004452-15) and ClinicalTrials.gov (NCT04724044). Patients were enrolled between Jan 25, 2021, and April 11, 2023, and 278 individuals were randomly allocated to receive standard of care in combination with either clarithromycin (n=139) or placebo (n=139). 134 patients in the clarithromycin group (five withdrew consent) and 133 patients in the placebo group (six withdrew consent) were included in the analysis of the primary endpoint. The primary endpoint was met in 91 (68%) patients in the clarithromycin group and 51 (38%) patients in the placebo group (difference 29·6% [95% CI 17·7-40·3]; odds ratio [OR] 3·40 [95% CI 2·06-5·63]; p<0·0001). Serious treatment-emergent adverse events (TEAEs) occurred in 58 (43%) patients in the clarithromycin group and 70 (53%) patients in the placebo group (difference 9·4% [95% CI -2·6 to 20·9]; OR 0·67 [95% CI 0·42 to 1·11]; p=0·14). None of the serious TEAEs was judged to be related to treatment assignment. Addition of clarithromycin to standard of care enhances early clinical response and attenuates the inflammatory burden of community-acquired pneumonia. The mechanism of benefit is associated with changes in the immune response. These findings suggest the importance of adding clarithromycin to β-lactams for treatment of patients in hospital with community-acquired pneumonia to achieve early clinical response and early decrease of the inflammatory burden. Hellenic Institute for the Study of Sepsis and Abbott Products Operations.

The Role of the Cumulative Illness Rating Scale (CIRS) in Estimating the Impact of Comorbidities on Chronic Obstructive Pulmonary Disease (COPD) Outcomes: A Pilot Study of the MACH (Multidimensional Approach for COPD and High Complexity) Study.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous systemic syndrome that often coexists with multiple comorbidities. In highly complex COPD patients, the role of the Cumulative Illness Rating Scale (CIRS) as a risk predictor of COPD exacerbation is not known. The objective of this study was determine the effectiveness of the CIRS score in detecting the association of comorbidities and disease severity with the risk of acute exacerbations in COPD patients. In total, 105 adults with COPD (mean age 72.1 ± 9.0 years) were included in this prospective study. All participants at baseline had at least two moderate exacerbations or one leading to hospitalization. The primary outcome was a composite of moderate or severe COPD exacerbation during the 12 months of follow-up. The CIRS indices (CIRS total score, Severity Index and Comorbidity Index) showed a positive correlation with modified Medical Research Council (mMRC), COPD assessment test (CAT) and a negative correlation with forced expiratory volume in the first second (FEV1), Forced Vital Capacity (FVC), and FEV1/FVC. The three CIRS indices were able to predict the 12-month rate of moderate or severe exacerbation (CIRS Total Score: Hazard Ratio (HR) = 1.12 (95% CI: 1.08-1.21); CIRS Severity Index: HR = 1.21 (95% CI: 1.12-1.31); CIRS Comorbidity Index = 1.58 (95% CI: 1.33-1.89)). Among patients with COPD, the comorbidity number and severity, as assessed by the CIRS score, influence the risk in moderate-to-severe exacerbations. The CIRS score also correlates with the severity of respiratory symptoms and lung function.

Immunosurveillance associated with upper respiratory symptoms in elite swimmers: The 8-month period leading into Commonwealth Games

ObjectivesTo monitor individual mucosal immunity and identify potential risk factors of upper respiratory symptoms in elite swimmers over a competitive season. DesignEight-month longitudinal study, observing mucosal immunity, Epstein–Barr virus status, training loads and illness symptoms of elite international swimmers, leading into the Commonwealth Games 2018. MethodsParticipants were fourteen elite swimmers (age ± standard deviation = 19.9 ± 0.8 years, height = 178.9 ± 6.3 cm, and mass = 75.0 ± 7.7 kg). Self-reported upper respiratory symptoms, training load and saliva samples were collected weekly. Venous blood samples were taken at study commencement to determine Epstein–Barr virus status. ResultsThroughout the study, 70 episodes of upper respiratory symptoms were recorded resulting in 34 days of missed training. Incidence (p = 0.001), severity (p = 0.022), and duration of upper respiratory symptoms (p = 0.001) were significantly higher during high training loads, compared to low. Eight swimmers (61 %) had evidence of past infection with Epstein–Barr virus, but this had no relationship with incidence, severity, or duration of upper respiratory symptoms (p > 0.05). Relative individual salivary immunoglobulin A concentration was 12 % lower when upper respiratory symptoms were present but was not statistically significant (p = 0.101). ConclusionsThis study highlights the importance of individual athlete monitoring, to identify swimmers at increased illness risk. Identification of possible risk factors for upper respiratory symptoms, such as increased training load, may allow for modifications in training or other illness preventative strategies for elite swimmers.

Inhalation Surfactant Therapy within Comprehensive Treatment of HIV-Infected Patients with Multiple Drug Resistant Tuberculosis

The objective: to evaluate the main eff ects of surfactant inhalations during the intensive phase of chemotherapy with the regimen containing bedaquiline and linezolid in HIV-infected patients with multiple drug resistant tuberculosis.Subjects and Methods. A single-center, open-label, controlled prospective cohort study was conducted. 80 patients with MDR-TB/HIV were enrolled in the study and randomized into two groups: ST+ Group included 40 patients who in addition to anti-tuberculosis therapy containing bedaquiline and linezolid during the intensive phase received inhalation of the suspension of Surfactant-BL according to a certain regimen. The course of 28 inhalations took 2 months, the total dose of surfactant was 700 mg. ST- Group included 40 patients who received anti-tuberculosis therapy only. To assess the severity of respiratory symptoms in patients, we used our own scoring. All patients also received antiretroviral therapy.Results. In the ST+ Group versus ST- Group, there was a decrease in the severity of tuberculosis clinical manifestations and timing of their relief, higher frequency of cavity healing by 21.2%, and faster sputum conversion by 28.6%. These rates are higher than in ST- Group and this is a short period of 10 weeks. None of the patients developed adverse reactions to surfactant inhalations. Patients tolerated well the combination of surfactant therapy, MDR TB chemotherapy containing bedaquiline and linezolid, and ART.

PEP-flute selfcare in epidemic respiratory infectious diseases – high societal impact at low cost?

Abstract Background The COVID-19 pandemic has led to worldwide increases in mortality and disrupted healthcare systems. The necessary countermeasures have adversely affected our lives, both mentally and economically. Home-based interventions to help individuals with early COVID-19 overcome the disease with fewer symptoms are needed. This study explored if self-care using positive expiratory pressure (PEP) as airway clearance is effective in reducing respiratory symptoms and, thus hypothetically prevent COVID-19 associated pneumonia. Methods This open-label, randomized trial (ClinicalTrials.gov:NCT04530435) recruited community dwelling adults from Capital Region and Region Zealand in Denmark from 6 Oct 2020 to 26 Feb 2021. Eligible participants (verified SARS-CoV-2 infection, COVID-19 symptoms, and able to perform self-care) were randomized to usual care or to PEP-flute self-care (PEP thrice daily) as an add-on to usual care. PEP-flutes were delivered by express mail and instructions given by video-links. The primary outcome was a change (analyzed by repeated measures mixed linear models) in self-reported symptom severity from baseline to day 30, as assessed by the COPD (chronic obstructive pulmonary disease) assessment test (CAT). Another outcome was the perceived effect of PEP-selfcare. Results The PEP self-care group (n = 190) had significantly lower symptom severity (group difference -1.2 points (95% confidence interval -2.1 to -0.2; p = 0.017)) at day 30 compared to the usual care group (n = 188). The PEP self-care group reported less chest tightness, less dyspnea, more vigor, and higher level of daily activity. When asked, “How do you describe the PEP-flute effect?”, 30% (n = 56) from the PEP group reported PEP-use to provoke coughing of phlegm. No serious adverse events were reported. Conclusions In early COVID-19, PEP-flute self-care was effective in reducing respiratory symptom severity among community dwelling adults and may have a future societal impact at a low cost. Key messages • We advocate for more research in self-care interventions to confirm if campaigns and handouts of PEP-flutes to mobilize the citizens’ selfcare are suitable public health responses to the next pandemic. • More research is needed to establish efficacy of non-drug interventions like PEP-selfcare for airway clearance to prevent pneumonia.

Correlation between pulmonary quantitative CT measurement indicators and respiratory symptoms in patients with chronic obstructive pulmonary disease in stable stage

Objective: To explore the correlation between pulmonary quantitative CT measurement indicators and respiratory symptoms in patients with stable chronic obstructive pulmonary disease (COPD). Methods: A total of 186 patients with COPD in stable stage who visited in the outpatient department of Beijing Hospital from March 2021 to February 2022 were prospectively included. Demographic data, respiratory symptoms and lung function were collected. The original DICOM data of high-resolution CT (HRCT) were processed using the FACT medical imaging information system and the pulmonary emphysema index pixel index-950 (PI-950) and the airway wall thickness (4-6 T) and the percentage of airway area (4-6 WA%) of the 4-6 generation bronchi which represent the segmental and subsegmental bronchi were measured automatically. According to the modified British medical research council dyspnea scale (mMRC, 0-1 point for low score group, 2-4 points for high score group), chronic obstructive pulmonary disease assessment test (CAT, score<10 points for low score group,≥10 points for high score group), cough, expectoration and wheezing (asymptomatic group and symptomatic group), they were divided into two groups as dependent variables. The relationship between imaging parameters and the above symptoms was evaluated using a logistic regression model. Results: The study ultimately included 186 patients who met the inclusion criteria, including 162 males and 24 females, aged (68.9±9.3) years old. There were 83 patients in the high mMRC group, 120 patients in the high CAT group, 146 patients in the cough group, 154 patients in the expectoration group, and 65 patients in the wheezing group. The age and emphysema parameter PI-950 in the high score group of mMRC were higher than those in the low score group, while the percentage of the forced expiratory volume in 1 second (FEV1) predicted value (FEV1 pred) after medication, the percentage of carbon monoxide diffusion volume (DLCO) predicted value (DLCO pred), and the percentage of the maximum midexpiratory flow (MMEF) predicted value (MMEF pred) after medication were lower than those in the low score group (all P<0.05). The age of the high CAT group was higher than that of the low score group, while FEV1 pred and MMEF pred after medication were lower than those of the low score group (all P<0.05). The proportion of males, patients with smoking history, and smoking index in the cough group were higher than those in the non cough group, while the 4 WA% was lower than that in the non cough group (all P<0.05). The proportion of males, patients with smoking history, smoking index, and PI-950 in the expectoration group were higher than those in the non expectoration group, while FEV1 pred after medication and 4 WA% were lower than those in the non expectoration group (all P<0.05). The 5 WA% and 6 WA% of the wheezing group were higher than those of the non wheezing group, while MMEF pred after medication was lower than that of the non wheezing group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for demographic characteristics, smoking, combined diseases, lung function and other confounding factors, for every 10% increase in PI-950, the likelihood of developing more severe dyspnea for the patients (high score group according to mMRC) increased by 67.3% (OR=1.673, 95%CI: 1.052-2.658); Every 10% increase in 6WA% increased the likelihood of wheezing by 3.189 times (OR=4.189, 95%CI: 1.070-16.395). No correlation was found between various imaging indicators and cough, expectoration, and CAT scores (P>0.05). Conclusion: Quantitative CT measurement indicators in stable COPD patients can explain the presence and severity of respiratory symptoms, the pulmonary emphysema indicator is associated with dyspnea, and the percentage of proximal airway wall area is associated with wheezing.