Severity Of Respiratory Symptoms Research Articles

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.
 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.
 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.
 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.
 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.

Respiratory virus surveillance in hospitalized children less than two-years of age in Kenema, Sierra Leone during the COVID-19 pandemic (October 2020- October 2021).

Globally, viral pathogens are the leading cause of acute respiratory infection in children under-five years. We aim to describe the epidemiology of viral respiratory pathogens in hospitalized children under-two years of age in Eastern Province of Sierra Leone, during the second year of the SARS-CoV-2 pandemic. We conducted a prospective study of children hospitalized with respiratory symptoms between October 2020 and October 2021. We collected demographic and clinical characteristics and calculated each participant´s respiratory symptom severity. Nose and throat swabs were collected at enrollment. Total nucleic acid was purified and tested for multiple respiratory viruses. Statistical analysis was performed using R version 4.2.0 software. 502 children less than two-years of age were enrolled. 376 (74.9%) had at least one respiratory virus detected. The most common viruses isolated were HRV/EV (28.2%), RSV (19.5%) and PIV (13.1%). Influenza and SARS-CoV-2 were identified in only 9.2% and 3.9% of children, respectively. Viral co-detection was common. Human metapneumovirus and RSV had more than two-fold higher odds of requiring O2 therapy while hospitalized. Viral pathogen prevalence was high (74.9%) in our study population. Despite this, 100% of children received antibiotics, underscoring a need to expand laboratory diagnostic capacity and to revisit clinical guidelines implementation in these children. Continuous surveillance and serologic studies among more diverse age groups, with greater geographic breadth, are needed in Sierra Leone to better characterize the long-term impact of COVID-19 on respiratory virus prevalence and to better characterize the seasonality of respiratory viruses in Sierra Leone.

Asthma in Pregnancy.

Asthma is a common chronic respiratory condition that affects approximately 10% of adult women in the United States. Pregnancy can present unique challenges for women with asthma, as changes in the body can alter the severity and management of asthma-related respiratory symptoms. In this article, we review the current understanding of asthma during pregnancy, including the direct effects of the disease state on the pregnant woman and fetus, risk factors for poor control of disease, as well as current treatment recommendations.

Factors that predict pursuing sinus surgery in the era of highly effective modulator therapy.

Comorbid chronic rhinosinusitis (CRS) remains unresolved for many people with cystic fibrosis (PwCF). While highly effective modulator therapy improves quality-of-life and symptom severity, the impact of this intervention and other factors associated with pursuing endoscopic sinus surgery (ESS) remains understudied. Adult PwCF + CRS were enrolled into a prospective, observational, multi-institutional study. Participants completed validated outcome measures to evaluate respiratory symptom severity, depression, headache, and sleep quality, as well as nasal endoscopy, sinus computed tomography (CT), and olfactory testing. Bivariate comparisons and regression modeling evaluated treatment cofactors, disease characteristics, and outcome measures associated with pursuing ESS. Sixty PwCF were analyzed, including 24 (40%) who elected ESS. Pursuing ESS was associated with worse SinoNasal Outcome Test (SNOT-22) total, rhinologic, psychological, and sleep dysfunction domain scores; worse Patient Health Questionnaire-9-Revised depression scores; worse Pittsburgh Sleep Quality Index total scores; worse weight, role, emotion, and eating domain scores on the Cystic Fibrosis Questionnaire-Revised; more severe disease on nasal endoscopy; and lack of modulator therapy (all p<0.050). Multivariable regression identified that worse SNOT-22 total score was associated with electing ESS (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.16, p=0.015) and elexacaftor/tezacaftor/ivacaftor (ETI) treatment (OR 0.04, 95% CI 0.004-0.34, p=0.004) was associated with pursing medical therapy. Worse sinonasal symptom burden, lack of ETI treatment, sleep quality, depression, and nasal endoscopy scores were associated with electing ESS, while lung disease severity and sinus CT scores were not. ETI use was associated with lower odds of pursuing ESS independent of sinonasal symptom burden.

Children Learning About Secondhand Smoke (CLASS III): a protocol for a cluster randomised controlled trial of a school-based smoke-free intervention in Bangladesh and Pakistan

IntroductionSecondhand smoke (SHS) exposure is a major cause of premature death and disease, especially among children. Children in economically developing countries are particularly affected as smoke-free laws are typically only...

Comparative analysis of machine learning approaches for predicting respiratory virus infection and symptom severity.

Respiratory diseases are among the major health problems causing a burden on hospitals. Diagnosis of infection and rapid prediction of severity without time-consuming clinical tests could be beneficial in preventing the spread and progression of the disease, especially in countries where health systems remain incapable. Personalized medicine studies involving statistics and computer technologies could help to address this need. In addition to individual studies, competitions are also held such as Dialogue for Reverse Engineering Assessment and Methods (DREAM) challenge which is a community-driven organization with a mission to research biology, bioinformatics, and biomedicine. One of these competitions was the Respiratory Viral DREAM Challenge, which aimed to develop early predictive biomarkers for respiratory virus infections. These efforts are promising, however, the prediction performance of the computational methods developed for detecting respiratory diseases still has room for improvement. In this study, we focused on improving the performance of predicting the infection and symptom severity of individuals infected with various respiratory viruses using gene expression data collected before and after exposure. The publicly available gene expression dataset in the Gene Expression Omnibus, named GSE73072, containing samples exposed to four respiratory viruses (H1N1, H3N2, human rhinovirus (HRV), and respiratory syncytial virus (RSV)) was used as input data. Various preprocessing methods and machine learning algorithms were implemented and compared to achieve the best prediction performance. The experimental results showed that the proposed approaches obtained a prediction performance of 0.9746 area under the precision-recall curve (AUPRC) for infection (i.e., shedding) prediction (SC-1), 0.9182 AUPRC for symptom class prediction (SC-2), and 0.6733 Pearson correlation for symptom score prediction (SC-3) by outperforming the best leaderboard scores of Respiratory Viral DREAM Challenge (a 4.48% improvement for SC-1, a 13.68% improvement for SC-2, and a 13.98% improvement for SC-3). Additionally, over-representation analysis (ORA), which is a statistical method for objectively determining whether certain genes are more prevalent in pre-defined sets such as pathways, was applied using the most significant genes selected by feature selection methods. The results show that pathways associated with the 'adaptive immune system' and 'immune disease' are strongly linked to pre-infection and symptom development. These findings contribute to our knowledge about predicting respiratory infections and are expected to facilitate the development of future studies that concentrate on predicting not only infections but also the associated symptoms.

Markers of limbic system damage following SARS-CoV-2 infection.

Alterations of the limbic system may be present in the chronic phase of SARS-CoV-2 infection. Our aim was to study the long-term impact of this disease on limbic system-related behaviour and its associated brain functional connectivity, according to the severity of respiratory symptoms in the acute phase. To this end, we investigated the multimodal emotion recognition abilities of 105 patients from the Geneva COVID-COG Cohort 223 days on average after SARS-CoV-2 infection (diagnosed between March 2020 and May 2021), dividing them into three groups (severe, moderate or mild) according to respiratory symptom severity in the acute phase. We used multiple regressions and partial least squares correlation analyses to investigate the relationships between emotion recognition, olfaction, cognition, neuropsychiatric symptoms and functional brain networks. Six to 9 months following SARS-CoV-2 infection, moderate patients exhibited poorer recognition abilities than mild patients for expressions of fear (P = 0.03 corrected), as did severe patients for disgust (P = 0.04 corrected) and irritation (P < 0.01 corrected). In the whole cohort, these performances were associated with decreased episodic memory and anosmia, but not with depressive symptoms, anxiety or post-traumatic stress disorder. Neuroimaging revealed a positive contribution of functional connectivity, notably between the cerebellum and the default mode, somatosensory motor and salience/ventral attention networks. These results highlight the long-term consequences of SARS-Cov-2 infection on the limbic system at both the behavioural and neuroimaging levels.

RWD59 Association of Time of Loss of Ambulation with Severity of Respiratory Symptoms in Patients with Nonsense Mutation Duchenne Muscular Dystrophy (NMDMD)

Age at loss of ambulation (AALoA) and respiratory symptoms for nmDMD have been compared between patients receiving ataluren from the STRIDE registry and standard of care (SoC) from the CINRG study. A 4-year delay in loss of ambulation (LoA) was demonstrated for ataluren-treated patients. However, estimating treatment effects on respiratory function is challenging due to data limitations. This study aimed to assess the association between LoA and respiratory function - defined by predicted forced vital capacity (pFVC).

0542 Obstructive sleep apnea in outpatients with COPD at Can Tho University of Medicine and Pharmacy Hospital – An Observational Study

Abstract Introduction The concurrence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is generally identified as overlap syndrome.This study evaluated biometric characteristics, sleep disorders, and scores comorbidities on OS and OSA groups in outpatients at the Respiratory Units of Can Tho University of Medicine and Pharmacy Hospital (RU-CTUMP); surveyed respiratory symptom severity, airway obstruction, and aerosol treatment characteristics in OS patients; and determined the correlations between sleep disorder severity and specific patient characteristics. Methods A cross-sectional, single-center descriptive study was conducted. We enrolled 48 outpatients at the RU-CTUMP in the study in three months. The patients were divided into two groups with overlapped COPD and OSA (OS, n = 30) vs. OSA-only (n = 18). Patients were asked to complete the demographic questionnaires, Epworth Sleepiness Scale (ESS) scores, STOP-Bang questionnaire, and Snoring Severity Scale (SSS). They were assessed for pulmonary function tests (PFTs) to confirm their COPD diagnosis, overnight respiratory polygraphy (Nox T3x), and Apnea-Hypopnea Index (AHI) to evaluate the severity of OSA, Charlson index to evaluate comorbidities, and their medication history. Results In the OS group, 100% of the patients suffered from dyspnea with the mean mMRC scores of 2.83 ± 0.75, mean FEV1 was 60.07 ± 23.09%, and 86% received inhaled medicine. In both groups, all participants suffered from 1 - ≥ 2 comorbidities. Overlapped patients had more comorbidities than OSA-only patients (Charlson scores of 2.33 and 1.17, respectively). There were significant correlations between the AHI value and the body mass index, neck circumferences, STOP-Bang score, the value of the Snoring Severity Scale, and minimum SpO2 (r = 0.45, 0.43, 0.46, 0.44, -0.69, respectively). In addition, COPD was a risk factor for OSA (OR = 1.125). Conclusion Home sleep testing in outpatients with COPD in RU-CTUMP revealed an increased prevalence of OSA compared to the OSA-only group. One of the most common comorbidities in individuals with overlap syndrome is hypertension, which is at least as common as in sleep apneic-only patients and may contribute to the disease's overall severity and prognosis. Support (if any)

Do adipocytes serve as a reservoir for SARS-CoV-2?

Obesity is associated with a higher risk of severe COVID-19 and increased mortality. In the current study, we have investigated the expression of ACE2, NRP1, and HMGB1, known to facilitate SARS-CoV-2 cell entry, in adipose tissue from non-COVID-19 control patients with normal weight, overweight and obesity. All factors were expressed, but no significant differences between the groups were observed. Furthermore, diabetes status and medications did not affect the expression of ACE2. Only in obese men, the expression of ACE2 in adipose tissue was higher than in obese women. In adipose tissue from patients that died from COVID-19, SARS-CoV-2 was detected in the adipocytes even though the patients died more than three weeks after the acute infection. This suggests that adipocytes may act as reservoirs for the virus. In COVID-19 patients, the expression of NRP1 was increased in COVID-19 patients with overweight and obesity. Furthermore, we observed an increased infiltration with macrophages in the COVID-19 adipose tissues compared to control adipose tissue. In addition, crown-like structures of dying adipocytes surrounded by macrophages were observed in the adipose tissue from COVID-19 patients. These data suggest that in obese individuals, in addition to an increased mass of adipose tissue that could potentially be infected, increased macrophage infiltration due to direct infection with SARS-CoV-2 and sustained viral shedding, rather than preinfection ACE2 receptor expression, may be responsible for the increased severity and mortality of COVID-19 in patients with obesity.

Exploring genetic associations between allergic diseases and indicators of COVID-19 using mendelian randomization

We carried out a bidirectional Mendelian randomization (MR) including cases ofeczema (N= 218,792), asthma (N= 462,933), and allergic rhinitis (N= 112,583). COVID-19 susceptibility (N= 1,683,768), COVID-19 hospitalization (N= 1,887,658), and COVID-19 severe respiratory symptom (N= 1,388,342) were sampled from GWAS database. The MR analysis was primarily based on inverse variance weighted (IVW), supplemented by several other algorithms. In the bidirectional MR analysis, eczema was negatively associated with COVID-19 susceptibility (odds ratio (OR) IVW= 0.92; p= 0.031) and COVID-19 hospitalization (ORIVW= 0.81, p= 0.010); asthma was negatively associated with COVID-19 susceptibility (ORIVW= 0.65, p= 0.005) and COVID-19 severe respiratory symptom (ORIVW= 0.20, p= 0.001). No significant association was found between allergic rhinitis and COVID-19 susceptibility (ORIVW= 0.80, p= 0.174), COVID-19 hospitalization (ORIVW= 0.71, p= 0.207), or COVID-19 severe respiratory symptom (ORIVW= 0.56; p= 0.167). The reverse MR analysis showed no potential reverse causal association. Our findings provided new evidence that allergic diseases might be associated with different risks of COVID-19 susceptibility, hospitalization, and severe respiratory symptom.