Use of a novel microbiome modulator improves anticancer immunity in a murine model of malignant pleural mesothelioma.

Objective: Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact of a novel microbiome modulator compound (MMC) on the gut microbiota composition, tumor immune microenvironment, and cancer control in a model of malignant pleural mesothelioma. Methods: Age- and weight-matched immunocompetent (n = 23) or athymic BALB/c mice (n = 15) were randomly assigned to MMC or no treatment (control) groups. MMC (31 ppm) was administered through the drinking water 14 days before AB12 malignant mesothelioma cell inoculation into the pleural cavity. The impact of MMC on tumor growth, animal survival, tumor-infiltrating leucocytes, gut microbiome, and fecal metabolome was evaluated and compared with those of control animals. Results: The MMC delayed tumor growth and significantly prolonged the survival of immunocompetent animals (P = .0015) but not that of athymic mice. The improved tumor control in immunocompetent mice correlated with increased infiltration of CD3+CD8+GRZB+ cytotoxic T lymphocytes in tumors. Gut microbiota analyses indicated an enrichment in producers of short chain fatty acids in MMC-treated animals. Finally, we observed a positive correlation between the level of fecal short chain fatty acids and abundance of tumor-infiltrating cytotoxic T cells in malignant pleural mesothelioma. Conclusions: MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.

Physical activity and lung function association in a healthy community-dwelling European population.

BACKGROUND: The association of physical activity (PA) and lung function (LF) varies from no measurable effect to delayed LF decline. We assessed the association between accelerometery-assessed PA and LF in a sample of apparently healthy, community-dwelling subjects. METHODS: We included two cross-sectional studies using data from the PneumoLaus study (2014-17 and 2018-21), conducted in Lausanne, Switzerland. PA was assessed by accelerometry and categorised as inactivity, light, moderate or vigorous. Forced expiratory volume in 1 second (FEV1), forced volume capacity (FVC) and maximal mid-expiratory flow (MMEF) were measured by spirometry and expressed in percentage of predicted value (PV). RESULTS: Overall, 1'910 (54.7% women, 62.0 ± 9.7 years) and 1'174 (53.4% women, 65.8 ± 9.5 years) participants were included in the first and the second surveys, respectively. In both surveys, moderate and vigorous PA showed a weak but significant correlation with FEV1 in percentage (PV) (R = 0.106 and 0.132 for the first and 0.111 and 0.125 for the second surveys, p < 0.001). Similar correlations with FVC (p < 0.001) were found. Associations held irrespective of smoking status and remained after multivariable adjustment. Fewer associations were detected between LF and light PA or between MMEF and PA. CONCLUSION: Moderate and vigorous intensity PA are associated with increased LF regardless of smoking status in apparently healthy community-dwelling European population. These associations are statistically but not clinically significant due to the small correlation coefficients (R < 0.30), corresponding to a weak association.

Associations of depressive and anxiety disorders with pulmonary disorders in the community - the PneumoLaus and PsyCoLaus studies.

INTRODUCTION: Mental health disorders figure among the many comorbidities of obstructive respiratory diseases. The multisystemic characteristics of chronic respiratory disease and its impact on quality of life could affect depressive and/or anxiety disorders. We aimed to evaluate the association of spirometric indices, ventilatory disorders and self-reported respiratory diseases with psychiatric disorders considering potential confounders. METHODS: We analysed data from CoLaus|PsyCoLaus, a Swiss population-based cohort study, consisting of 2'774 participants (56% women; mean age: 62.3 (SD=±9.9) years) who performed spirometry and completed semi-structured psychiatric interviews. We defined ventilatory disorders using GLI-2012 references. Major depressive episode (MDE) and anxiety disorders were defined using the DSM-IV (Diagnostic and Statistical Manual). RESULTS: 630 subjects (22.7%) presented a recent MDE. Reversible obstructive ventilatory disorders were associated with recent MDE (OR=1.94, 95% CI95 1.10-3.43) and recent anxiety disorders (2.21 [1.16-4.22]) only in unadjusted model. Self-reported COPD and asthma were associated with MDE with ORs of 2.49 (95%CI, 1.19-5.27) and 1.56 (95% CI, 1.04-2.35) after adjustment, respectively. Possible restrictive ventilatory impairment was positively associated with recent anxiety disorders (OR=2.46, 1.10-5.51). Z-scores of FEV1, FVC and maximum mid expiratory flow (MMEF) were not associated with psychiatric disorders. There was no association between ventilatory disorders and MDE in adjusted models. CONCLUSIONS: In this cross-sectional population-based study, the association between respiratory disorders and depressive disorders was observed for self-reported COPD and asthma, but not with objective diagnoses based on spirometry. Lung volumes are not associated with psychiatric disorders. Further prospective studies will be necessary to understand the significance of the association.

[Lung cancer screening : towards the implementation of a pilot project in Switzerland]. / Dépistage du cancer pulmonaire : vers l'implémentation d'un projet pilote en Suisse.

Lung cancer is responsible for one in five cancer-related deaths. Screening for lung cancer using low-dose chest CT (LDCT) is supported by several international studies targeting the at-risk population as part of an organised programme. Given the organisational challenges for the healthcare systems of the countries concerned, this involves setting up pilot screening projects. This requires close collaboration between the players involved, with a multidisciplinary approach structured around the participant, aiming to offer the expertise of the pulmonologist and the radiologist on the LDCT performed, interpreted with the help of artificial intelligence. Here we set out the elements needed to develop a screening programme, starting with the implementation of a pilot project.

Le cancer pulmonaire est responsable d'un décès lié au cancer sur cinq. Le dépistage du cancer pulmonaire par le scanner thoracique à faible dose (LDCT) est soutenu par plusieurs études internationales ciblant la population à risque dans le cadre d'un programme organisé. Vu les enjeux organisationnels pour le système de santé des pays concernés, cela passe par la mise en place de projets pilotes de dépistage. Cela requiert une collaboration étroite entre les différents acteurs, avec une approche multidisciplinaire structurée autour du participant visant à offrir l'expertise du pneumologue et du radiologue sur le LDCT effectué, interprété avec l'aide de l'intelligence artificielle. Nous exposons ici les éléments nécessaires à l'élaboration d'un programme de dépistage, en passant d'abord par la mise en place d'un projet pilote.

Clinical characteristics governing treatment adjustment in COPD patients: results from the Swiss COPD cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a widespread chronic disease characterised by irreversible airway obstruction [1]. Features of clinical practice and healthcare systems for COPD patients can vary widely, even within similar healthcare structures. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy is considered the most reliable guidance for the management of COPD and aims to provide treating physicians with appropriate insight into the disease. COPD treatment adaptation typically mirrors the suggestions within the GOLD guidelines, depending on how the patient has been categorised. However, the present study posits that the reasons for adjusting COPD-related treatment are hugely varied. OBJECTIVES: The objective of this study was to assess the clinical symptoms that govern both pharmacological and non-pharmacological treatment changes in COPD patients. Using this insight, the study offers suggestions for optimising COPD management through the implementation of GOLD guidelines. METHODS: In this observational cohort study, 24 general practitioners screened 260 COPD patients for eligibility from 2015-2019. General practitioners were asked to collect general information from patients using a standardised questionnaire to document symptoms. During a follow-up visit, the patient's symptoms and changes in therapy were assessed and entered into a central electronic database. Sixty-five patients were removed from the analysis due to exclusion criteria, and 195 patients with at least one additional visit within one year of the baseline visit were included in the analysis. A change in therapy was defined as a change in either medication or non-medical treatment, such as pulmonary rehabilitation. Multivariable mixed models were used to identify associations between given symptoms and a step up in therapy, a step down, or a step up and a step down at the same time. RESULTS: For the 195 patients included in analyses, a treatment adjustment was made during 28% of visits. In 49% of these adjustments, the change in therapy was a step up, in 33% a step down and in 18% a step up (an increase) of certain treatment factors and a step down (a reduction) of other prescribed treatments at the same time. In the multivariable analysis, we found that the severity of disease was linked to the probability of therapy adjustment: patients in GOLD Group C were more likely to experience an increase in therapy compared to patients in GOLD Group A (odds ratio [OR] 3.43 [95% confidence interval {CI}: 1.02-11.55; p = 0.135]). In addition, compared to patients with mild obstruction, patients with severe (OR 4.24 [95% CI: 1.88-9.56]) to very severe (OR 5.48 [95% CI: 1.31-22.96]) obstruction were more likely to experience a therapy increase (p <0.0001). Patients with comorbidities were less likely to experience a treatment increase than those without (OR 0.42 [95% CI: 0.24-0.73; p = 0.002]). A therapy decrease was associated with both a unit increase in COPD Assessment Test (CAT) score (OR 1.07 [95% CI: 1.01-1.14; p = 0.014]) and having experienced an exacerbation (OR 2.66 [95% CI: 1.01-6.97; p = 0.047]). The combination of steps up as well as steps down in therapy was predicted by exacerbation (OR 8.93 [95% CI: 1.16-68.28; p = 0.035]) and very severe obstruction (OR 589 [95% CI: 2.72 - >999; p = 0.109]). CONCLUSIONS: This cohort study provides insight into the management of patients with COPD in a primary care setting. COPD Group C and airflow limitation GOLD 3-4 were both associated with an increase in COPD treatment. In patients with comorbidities, there were often no treatment changes. Exacerbations did not make therapy increases more probable. The presence of neither cough/sputum nor high CAT scores was associated with a step up in treatment.

Adherence to the GOLD Guidelines in Primary Care: Data from the Swiss COPD Cohort.

(1) Introduction: Chronic obstructive pulmonary disease (COPD) and its associated morbidity and mortality are a global burden on both affected patients and healthcare systems. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) issues guidelines with the aim of improving COPD management. Previous studies reported significant variability in adherence to these recommendations. The objective of this study was to evaluate Swiss primary practitioners' adherence to the GOLD guidelines for the pharmacological treatment of stable COPD. (2) Methods: We studied patients who were included in the Swiss COPD cohort study, an ongoing prospective study in a primary care setting, between 2015 and 2022. The key inclusion criteria are age ≥ 40 years, FEV1/FVC ratio < 70%, and a smoking history of at least 20 pack-years. Adherence to the GOLD guidelines was assessed per visit and over time. (3) Results: The data of 225 COPD patients (mean age 67 ± 9 years, 64% male) and their respective 1163 visits were analyzed. In 65% of visits (726/1121), treatment was prescribed according to the GOLD guidelines. Non-adherence was most common in GOLD groups A and B (64% and 33%) and mainly consisted of over-treatment (two long-acting bronchodilators in group A (98/195, 50%) and ICS in groups A (21/195, 11%) and B (198/808, 25%)). In group D, the prescriptions conformed with the guidelines in 99% of cases (109/108). Guideline adherence was associated with high symptom load (COPD Assessment Test) (OR 1.04, p = 0.002), high number of exacerbations (OR = 2.07, p < 0.001), asthma overlap (OR 3.36, p = 0.049), and diabetes mellitus (OR 2.82, p = 0.045). (4) Conclusion: These results confirm a conflict between the GOLD recommendations and primary practice, mainly concerning over-treatment in GOLD groups A and B. Patients with high symptom load, high exacerbation risk, asthma overlap, and diabetes mellitus are more likely to be treated in conformity with the guidelines. Further research is needed to uncover the reasons for the discrepancies and to design strategies for improvement.

Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations. Our objective was to describe recurrent exacerbations in a GP-based Swiss COPD cohort and develop a statistical model for predicting exacerbation. METHODS: COPD cohort demographic and medical data were recorded for 24 months, by means of a questionnaire-based COPD cohort. The data were split into training (75%) and validation (25%) datasets. A negative binomial regression model was developed using the training dataset to predict the exacerbation rate within 1 year. An exacerbation prediction model was developed, and its overall performance was validated. A nomogram was created to facilitate the clinical use of the model. RESULTS: Of the 229 COPD patients analyzed, 77% of the patients did not experience exacerbation during the follow-up. The best subset in the training dataset revealed that lower forced expiratory volume, high scores on the MRC dyspnea scale, exacerbation history, and being on a combination therapy of LABA + ICS (long-acting beta-agonists + Inhaled Corticosteroids) or LAMA + LABA (Long-acting muscarinic receptor antagonists + long-acting beta-agonists) at baseline were associated with a higher rate of exacerbation. When validated, the area-under-curve (AUC) value was 0.75 for one or more exacerbations. The calibration was accurate (0.34 predicted exacerbations vs 0.28 observed exacerbations). CONCLUSION: Nomograms built from these models can assist clinicians in the decision-making process of COPD care.

Characteristics of Severe Asthma Patients and Predictors of Asthma Control in the Swiss Severe Asthma Registry.

BACKGROUND: Asthma is a chronic airway disease, affecting over 300 million people worldwide. 5-10% of patients suffer from severe asthma and account for 50% of asthma-related financial burden. Availability of real-life data about the clinical course of severe asthma is insufficient. OBJECTIVES: The aims of this study were to characterize patients with severe asthma in Switzerland, enrolled in the Swiss Severe Asthma Registry (SSAR), and evaluate predictors for asthma control. METHOD: A descriptive characterisation of 278 patients was performed, who were prospectively enrolled in the registry until January 2022. Socio-demographic variables, comorbidities, diagnostic values, asthma treatment, and healthcare utilisation were evaluated. Groups of controlled and uncontrolled asthma according to the asthma control test were compared. RESULTS: Forty-eight percent of patients were female and the mean age was 55.8 years (range 13-87). The mean body mass index (BMI) was 27.4 kg/m2 (±6). 10.8% of patients were current smokers. Allergic comorbidities occurred in 54.3% of patients, followed by chronic rhinosinusitis (46.4%) and nasal polyps (34.1%). According to the ACT score, 54.7% had well controlled, 16.2% partly controlled and 25.9% uncontrolled asthma. The most common inhalation therapy was combined inhaled corticosteroids/long-acting ß2-agonists (78.8%). Biologics were administered to 81.7% of patients and 19.1% received oral steroids. The multivariable analysis indicated that treatment with biologics was positively associated with asthma control whereas higher BMI, oral steroids, exacerbations, and COPD were negative predictors for asthma control. CONCLUSION: Biologics are associated with improved control in severe asthma. Further studies are required to complete the picture of severe asthma in order to provide improved care for those patients.

[COPD : a still neglected condition]. / BPCO : une maladie encore négligée.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung disorder with a complex clinical picture. The diagnosis may be difficult at times, as COPD may develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in early detection of disease. Suspected COPD may be confirmed by further investigations in collaboration with a pulmonologist. The most recent GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. General practitioners are crucial for implementing non-pharmacological measures such as smoking cessation, regular exercise, vaccinations, and patient self-management education. However, this also underlines the challenges to implement the GOLD recommendations in daily practice.

La BPCO est une maladie hétérogène avec un tableau clinique complexe. Le diagnostic n'est pas toujours facile à évoquer, car elle peut se développer insidieusement et passer longtemps inaperçue. Les médecins de premier recours (MPR) jouent donc un rôle central dans le diagnostic précoce. La suspicion de BPCO peut être confirmée en collaboration avec un pneumologue par des examens fonctionnels respiratoires avant l'instauration d'un traitement médicamenteux. Les nouvelles recommandations GOLD, publiées en 2022 définissent trois groupes de risques pour la BPCO (A-B-E). Les MPR sont importants pour la mise en œuvre de mesures accompagnant le traitement (arrêt du tabac, activité physique régulière, vaccinations, éducation thérapeutique). Mais cela souligne également les exigences élevées de la mise en œuvre des recommandations GOLD dans la pratique quotidienne.*.

Prevalence of small airway dysfunction in the Swiss PneumoLaus Cohort.

Background: Recent evidence identified exposure to particulate matter of size ≤2.5 µm (PM2.5) as a risk factor for high prevalence of small airway dysfunction (SAD). We assessed the prevalence of SAD in a European region with low air pollution levels. Methods: SAD was defined as a maximum mid-expiratory flow (MMEF) <65% of predicted value (PV) or MMEF 65 years only. In an area where ambient PM2.5 concentration was <15 µg·m-3 during the observation period (2010 and 2020), ≥72% of participants with SAD were ever-smokers. Conclusions: The observed low prevalence of SAD of 5.0-12.7% depending on criteria employed may be related to lower PM2.5 exposure. Smoking was the main factor associated with SAD in an area with low PM2.5 exposure. Employing a MMEF threshold <65% PV carries a risk of SAD overdiagnosis in elderly individuals.

[COPD - An Underestimated Disease]. / COPD ­ eine unterschätzte Erkrankung.

COPD - An Underestimated Disease Abstract: Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition with a complex clinical picture. The diagnosis is not easy to make because COPD can develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in the early detection of the disease. Suspected COPD can be confirmed by special examinations in collaboration with pulmonologists. The new GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. A short- or long-acting bronchodilator (SAMA/SABA or LAMA/LABA) is recommended for group A, and a dual long-acting bronchodilator therapy (LABA+LAMA) is recommended for group B and E. In case of blood eosinophilia (≥300 cells/µl) and/or recent hospitalization for COPD exacerbation, triple therapy (LABA+LAMA+ICS) is recommended. General practitioners are important in implementing non-pharmacological measures (smoking cessation, regular exercise, vaccinations, patient selfmanagement education). However, this also underlines the high demands of the implementation of the GOLD guideline in daily practice.

Azithromycin alters spatial and temporal dynamics of airway microbiota in idiopathic pulmonary fibrosis.

Background: High bacterial burden in the lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin (AZT) is a macrolide antibiotic known to alter the lung microbiota in several chronic pulmonary diseases, and observational studies have shown a positive effect of AZT on mortality and hospitalisation rate in IPF. However, the effect of AZT on the lung microbiota in IPF remains unknown. Methods: We sought to determine the impact of a 3-month course of AZT on the lung microbiota in IPF. We assessed sputum and oropharyngeal swab specimens from 24 adults with IPF included in a randomised controlled crossover trial of oral AZT 500 mg 3 times per week. 16S rRNA gene amplicon sequencing and quantitative PCR (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARGs) were assessed using real-time qPCR. Results: AZT significantly decreased community diversity with a stronger and more persistent effect in the lower airways (sputum). AZT treatment altered the temporal kinetics of the upper (oropharyngeal swab) and lower airway microbiota, increasing community similarity between the two sites for 1 month after macrolide cessation. Patients with an increase in ARG carriage had lower bacterial density and enrichment of the genus Streptococcus. In contrast, patients with more stable ARG carriage had higher bacterial density and enrichment in Prevotella. Conclusions: AZT caused sustained changes in the diversity and composition of the upper and lower airway microbiota in IPF, with effects on the temporal and spatial dynamics between the two sites.

Long-Term Consequences of COVID-19: A 1-Year Analysis.

Long-lasting symptoms after SARS-CoV-2 infection have been described many times in the literature and are referred to as Long COVID. In this prospective, longitudinal, monocentric, observational study, we collected the health complaints of 474 patients (252 ambulatory and 222 hospitalized) at Lausanne University Hospital 1 year after COVID-19 diagnosis. Using a self-reported health survey, we explored cardiopulmonary, vascular, neurological, and psychological complaints. Our results show that age, Charlson comorbidity index, and smoking habits were associated with hospital admission. Regarding the vascular system, we found that having had thromboembolism before SARS-CoV-2 infection was significantly associated with a higher risk of recurrence of thromboembolism at 1 year. In the neurologic evaluation, the most frequent symptom was fatigue, which was observed in 87.5% of patients, followed by "feeling slowed down", headache, and smell disturbance in 71.5%, 68.5%, and 60.7% of cases, respectively. Finally, our cohort subjects scored higher overall in the STAI, CESD, Maastricht, and PSQI scores (which measure anxiety, depression, fatigue, and sleep, respectively) than the healthy population. Using cluster analysis, we identified two phenotypes of patients prone to developing Long COVID. At baseline, CCS score, prior chronic disease, stroke, and atrial fibrillation were associated with Long COVID. During COVID infection, mechanical ventilation and five neurological complaints were also associated with Long COVID. In conclusion, this study confirms the wide range of symptoms developed after COVID with the involvement of all the major systems. Early identification of risk factors associated with the development of Long COVID could improve patient follow-up; nevertheless, the low specificity of these factors remains a challenge to building a systematic approach.

[Granulomatosis with polyangiitis: what's new?] / Granulomatose avec polyangéite : quoi de neuf ?

Within the group of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (GPA) is the most frequent. The incidence is around 10 to 20 cases/million/year. Clinical manifestations are varied, with ENT, lungs and kidneys most frequently involved. ANCA are pathogenic by triggering neutrophil activation, which leads to vascular damage. Detection of ANCA is most helpful in establishing the diagnosis, but serology may be negative in GPA limited to the airways. Diagnostic work-up and therapy require a multidisciplinary approach. Treatment includes an induction and maintenance phase, combining corticosteroids and immunosuppressive drugs. It aims at limiting the risk of relapses, which is important in GPA, and at reducing corticosteroids toxicity.

La granulomatose avec polyangéite (GPA) fait partie des vasculites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA). La maladie touche principalement la sphère ORL, les poumons et les reins. Son incidence est de 10 à 20 cas/million/année. Les ANCA sont pathogéniques en induisant une activation des polynucléaires neutrophiles, entraînant des lésions endothéliales. Le diagnostic est facilité par la détection des ANCA, qui peuvent cependant être absents dans les formes ORL limitées. La prise en charge est multidisciplinaire. Le traitement comprend une phase d'induction et une autre de maintien de la rémission, associant corticostéroïdes et immunosuppresseurs. L'objectif du traitement est de limiter le risque important de rechute et de réduire la toxicité des corticostéroïdes.

Performance of microbiological tests for tuberculosis diagnostic according to the type of respiratory specimen: A 10-year retrospective study.

Background: The microbial diagnosis of tuberculosis (TB) remains challenging and relies on multiple microbiological tests performed on different clinical specimens. Polymerase chain reactions (PCRs), introduced in the last decades has had a significant impact on the diagnosis of TB. However, questions remain about the use of PCRs in combination with conventional tests for TB, namely microscopy and culture. We aimed to determine the performance of microscopy, culture and PCR for the diagnosis of pulmonary tuberculosis according to the type of clinical specimen in order to improve the diagnostic yield and to avoid unnecessary, time and labor-intensive tests. Methods: We conducted a retrospective study (2008-2018) on analysis (34'429 specimens, 14'358 patients) performed in our diagnostic laboratory located in the Lausanne University Hospital to compare the performance of microbiological tests on sputum, induced sputum, bronchial aspirate and bronchoalveolar lavage (BAL). We analysed the performance using a classical "per specimen" approach and a "per patient" approach for paired specimens collected from the same patient. Results: The overall sensitivities of microscopy, PCR and culture were 0.523 (0.489, 0.557), 0.798 (0.755, 0.836) and 0.988 (0.978, 0.994) and the specificity were 0.994 (0.993, 0.995), 1 (0.999, 1) and 1 (1, 1). Microscopy displayed no significant differences in sensitivity according to the type of sample. The sensitivities of PCR for sputum, induced sputum, bronchial aspirate and BAL were, 0.821 (0.762, 0.871), 0.643 (0.480, 0.784), 0.837 (0.748, 0.904) and 0.759 (0.624, 0.865) respectively and the sensitivity of culture were, 0.993 (0.981, 0.998), 0.980 (0.931, 0.998), 0.965 (0.919, 0.988), and 1 (0.961, 1) respectively. Pairwise comparison of specimens collected from the same patient reported a significantly higher sensitivity of PCR on bronchial aspirate over BAL (p < 0.001) and sputum (p < 0.05) and a significantly higher sensitivity of culture on bronchial aspirate over BAL (p < 0.0001). Conclusions: PCR displayed a higher sensitivity and specificity than microscopy for all respiratory specimens, a rational for a smear-independent PCR-based approach to initiate tuberculosis microbial diagnostic. The diagnosis yield of bronchial aspirate was higher than BAL. Therefore, PCR should be systematically performed also on bronchial aspirates when available.

Home Use of Mechanical Insufflation/Exsufflation in Adult Patients in Western Switzerland.

BACKGROUND: Mechanical insufflation/exsufflation (MI-E) devices are often prescribed to patients with inefficient cough and recurrent infections, but their use in the home setting is not well characterized. OBJECTIVE: The objective of this study was to report a real-life experience and identify factors that are associated with home MI-E use in adult patients. METHODS: This is a cross-sectional observational study of adult subjects with neurological disease using MI-E at home for more than 3 months. RESULTS: A total of 43 patients were included. Median age (interquartile range) was 48 (31-64) years. The most common diagnosis was muscular dystrophy (n = 15), followed by multiple sclerosis (n = 7) and amyotrophic lateral sclerosis (n = 7). 24 subjects (56%) reported using the MI-E at least once weekly. Based on device data downloads, the median objective use was 23% of days analysed (approximately 2 times per week). The vast majority (94%) of all participants reported using the device at least daily during an infectious episode, while 62% reported having used the device in emergency situations such as bronchoaspiration. Reported use correlated well with objective use (r = 0.82). Most subjects reported an improvement in their respiratory health (64%) and were satisfied with the device (78%). Higher reported and objective use were associated with increased symptoms (p = 0.001) and higher satisfaction with the device (p = 0.008). We found no association between frequency of use and baseline cough peak flow (CPF), bulbar impairment, non-invasive ventilation use, living environment, or supervised administration. CONCLUSION: Regular home MI-E use was associated with greater symptom burden and overall satisfaction with the device and was not influenced by baseline CPF. Patients without substantial bronchorrhea might not use the MI-E regularly but might still need to use the device at home during acute events. Therefore, familiarity with the MI-E via appropriate and repeated practical training is crucial.

Radiation Exposure to Low-Dose Computed Tomography for Lung Cancer Screening: Should We Be Concerned?

Lung cancer screening (LCS) programs through low-dose Computed Tomography (LDCT) are being implemented in several countries worldwide. Radiation exposure of healthy individuals due to prolonged CT screening rounds and, eventually, the additional examinations required in case of suspicious findings may represent a concern, thus eventually reducing the participation in an LCS program. Therefore, the present review aims to assess the potential radiation risk from LDCT in this setting, providing estimates of cumulative dose and radiation-related risk in LCS in order to improve awareness for an informed and complete attendance to the program. After summarizing the results of the international trials on LCS to introduce the benefits coming from the implementation of a dedicated program, the screening-related and participant-related factors determining the radiation risk will be introduced and their burden assessed. Finally, future directions for a personalized screening program as well as technical improvements to reduce the delivered dose will be presented.

Personalized predictions of adverse side effects of the COVID-19 vaccines.

Background: Misconceptions about adverse side effects are thought to influence public acceptance of the Coronavirus disease 2019 (COVID-19) vaccines negatively. To address such perceived disadvantages of vaccines, a novel machine learning (ML) approach was designed to generate personalized predictions of the most common adverse side effects following injection of six different COVID-19 vaccines based on personal and health-related characteristics. Methods: Prospective data of adverse side effects following COVID-19 vaccination in 19943 participants from Iran and Switzerland was utilized. Six vaccines were studied: The AZD1222, Sputnik V, BBIBP-CorV, COVAXIN, BNT162b2, and the mRNA-1273 vaccine. The eight side effects were considered as the model output: fever, fatigue, headache, nausea, chills, joint pain, muscle pain, and injection site reactions. The total input parameters for the first and second dose predictions were 46 and 54 features, respectively, including age, gender, lifestyle variables, and medical history. The performances of multiple ML models were compared using Area Under the Receiver Operating Characteristic Curve (ROC-AUC). Results: The total number of people receiving the first dose of the AZD1222, Sputnik V, BBIBP-CorV, COVAXIN, BNT162b2, and mRNA-1273 were 6022, 7290, 5279, 802, 277, and 273, respectively. For the second dose, the numbers were 2851, 5587, 3841, 599, 242 and 228. The Logistic Regression model for predicting different side effects of the first dose achieved ROC-AUCs of 0.620-0.686, 0.685-0.716, 0.632-0.727, 0.527-0.598, 0.548-0.655, 0.545-0.712 for the AZD1222, Sputnik V, BBIBP-CorV, COVAXIN, BNT162b2 and mRNA-1273 vaccines, respectively. The second dose models yielded ROC-AUCs of 0.777-0.867, 0.795-0.848, 0.857-0.906, 0.788-0.875, 0.683-0.850, and 0.486-0.680, respectively. Conclusions: Using a large cohort of recipients vaccinated with COVID-19 vaccines, a novel and personalized strategy was established to predict the occurrence of the most common adverse side effects with high accuracy. This technique can serve as a tool to inform COVID-19 vaccine selection and generate personalized factsheets to curb concerns about adverse side effects.