A Prospective Hospital-Based Study of the Clinical Impact of Non-Severe Acute Respiratory Syndrome (Non-SARS)-Related Human Coronavirus Infection

Background. In addition to the human coronaviruses (HCoVs) OC43 and 229E, which have been known for decades to cause infection in humans, 2 new members of this genus have recently been identified: HCoVs NL63 and HKU1. Their impact as a cause of respiratory tract disease in adults at risk for complications needs to be established. Methods. We prospectively assessed the clinical impact of coronavirus infection (excluding cases of severe acute respiratory syndrome) among hospitalized adults. All patients with respiratory disease for whom bronchoalveolar lavage was performed were screened by reverse-transcriptase polymerase chain reaction for the presence of all 4 HCoVs. Results. HCoV was identified in 29 (5.4%) of 540 bronchoalveolar lavage fluid specimens from 279 subjects (mean age, 51 years; 63% male). HCoV OC43 was identified most frequently (12 isolates), followed by 229E (7 isolates), NL63 (6 isolates), and HKU1 (4 isolates). In all, 372 (69%) of 540 bronchoalveolar lavage fluid specimens were negative for bacteria, and 2 persons were coinfected with other respiratory viruses. Transplantation was the most common underlying condition. Of the 29 patients who had HCoV identified in their bronchoalveolar lavage fluid specimens, 9 (31%) were hospitalized in the intensive care unit, 22 (76%) presented to the hospital with acute respiratory symptoms, 16 (55%) presented with cough and/or sputum, 13 (45%) presented with dyspnea, 16 (55%) had experienced prior respiratory infection, and 18 (62%) had a new infiltrate that was visible on chest radiograph. The most frequent final diagnosis was a lower respiratory tract infection. Conclusions. The recently discovered HCoVs NL63 and HKU1 contribute significantly to the overall spectrum of coronavirus infection. Our study also suggests that coronaviruses contribute to respiratory symptoms in most case

New Respiratory Enterovirus and Recombinant Rhinoviruses among Circulating Picornaviruses

Increased genomic diversity of these viruses is demonstrated

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation.

Chronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described. LT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis. Among patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS. Although these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach

Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract Infections

Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5′UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers

The pandemic toll and post-acute sequelae of SARS-CoV-2 in healthcare workers at a Swiss University Hospital.

Healthcare workers have potentially been among the most exposed to SARS-CoV-2 infection as well as the deleterious toll of the pandemic. This study has the objective to differentiate the pandemic toll from post-acute sequelae of SARS-CoV-2 infection in healthcare workers compared to the general population. The study was conducted between April and July 2021 at the Geneva University Hospitals, Switzerland. Eligible participants were all tested staff, and outpatient individuals tested for SARS-CoV-2 at the same hospital. The primary outcome was the prevalence of symptoms in healthcare workers compared to the general population, with measures of COVID-related symptoms and functional impairment, using prevalence estimates and multivariable logistic regression models. Healthcare workers (n=3,083) suffered mostly from fatigue (25.5%), headache (10.0%), difficulty concentrating (7.9%), exhaustion/burnout (7.1%), insomnia (6.2%), myalgia (6.7%) and arthralgia (6.3%). Regardless of SARS-CoV-2 infection, all symptoms were significantly higher in healthcare workers than the general population (n=3,556). SARS-CoV-2 infection in healthcare workers was associated with loss or change in smell, loss or change in taste, palpitations, dyspnea, difficulty concentrating, fatigue, and headache. Functional impairment was more significant in healthcare workers compared to the general population (aOR 2.28; 1.76-2.96), with a positive association with SARS-CoV-2 infection (aOR 3.81; 2.59-5.60). Symptoms and functional impairment in healthcare workers were increased compared to the general population, and potentially related to the pandemic toll as well as post-acute sequelae of SARS-CoV-2 infection. These findings are of concern, considering the essential role of healthcare workers in caring for all patients including and beyond COVID-19

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Severe Dyspnea Is an Independent Predictor of Readmission or Death in COPD Patients Surviving Acute Hypercapnic Respiratory Failure in the ICU

Background: Predicting outcome after index admission in the ICU for COPD-related acute hypercapnic respiratory failure (AHRF) is difficult. Simple tools to stratify this risk and to promote interventions to mitigate it are needed.Aim: To prospectively evaluate the ability of severe dyspnea (NYHAIII-IV) to predict hospital readmission or death in COPD patients surviving AHRF in the ICU.Methods: 50 consecutive COPD patients were recruited from a larger cohort of patients (n = 78) surviving AHRF in the ICU. All predictive variables were collected within 15 days after resolution of respiratory failure before hospital discharge. COPD was diagnosed by spirometry. Heart failure was diagnosed with clinical rules and echocardiography. NYHA was measured upon hospital discharge. Hospital readmission and death were recorded at regular intervals for 3 months.Results: 21/50 (42%) COPD patients died or were readmitted to the hospital during the observation period: 12 out of the 20 NYHA III-IV patients (60%) and 8 out of the 28 NYHA I-II patients (29%). NYHA III-IV was associated with risk of readmission or death (univariate HR: 2.73, IC95: 1.11–6.69, p = 0.028). After controlling for age, FEV1, heart failure and BMI, NYHA III-IV remained associated with readmission or death (multivariate HR: 2.71, IC95: 1.06–6.93, p = 0.038).Conclusions: Our findings suggest that severe dyspnea measured upon hospital discharge in COPD patients surviving AHRF can stratify patient's risk of 3-month readmission or death

Asthme professionnel

L’asthme professionnel est la plus fréquente des maladies respiratoires professionnelles. Il touche surtout les travailleurs jeunes et a des conséquences socio-économiques importantes. Le reconnaître précocement permet d’améliorer le pronostic. Une investigation rigoureuse, pendant que le travailleur est encore exposé sur son lieu de travail, et un suivi médical approprié nécessitent une collaboration pluridisciplinaire. La prévention reste l’élément essentiel dans la prise en charge de cette maladie

Antibiotiques inhalés dans la prise en charge des bronchiectasies en dehors de la mucoviscidose

Bronchiectasis is irreversible bronchial dilatation associated with chronic respiratory symptoms. Management is aimed at reducing symptoms and slowing the progression of the disease by interrupting the vicious circle: bronchial infection, inflammation, altered mucociliary clearance, lung destruction. Unlike the literature on inhaled antibiotics in cystic fibrosis, literature data are limited and of low quality for bronchiectasis of other causes. However, new recommendations from the European Respiratory Society propose the conditional use of inhaled antibiotics to prevent repeated infectious exacerbations and to eradicate Pseudomonas aeruginosa colonization