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Non-tuberculous mycobacteria (NTM) include more than 160 ubiquitous, environmental, acid-fast-staining bacterial species, some of which may cause disease in humans. Chronic pulmonary infection is the most common clinical manifestation. Although patients suffering from chronic lung diseases are particularly susceptible to NTM pulmonary disease, many affected patients have no apparent risk factors. Host and pathogen factors leading to NTM pulmonary disease are not well understood and preventive therapies are lacking. NTM isolation and pulmonary disease are reported to rise in frequency in Europe as well as in other parts of the world. Differentiation between contamination, infection, and disease remains challenging. Treatment of NTM pulmonary disease is arduous, lengthy, and costly. Correlations between results of in vitro antibiotic susceptibility testing and clinical treatment outcomes are only evident for the Mycobacterium avium complex, M. kansasii, and some rapidly growing mycobacteria. We describe the epidemiology of NTM pulmonary disease as well as emerging NTM pathogens and their geographical distribution in non-cystic fibrosis patients in Europe. We also review recent innovations for the diagnosis of NTM pulmonary disease, summarize treatment recommendations, and identify future research priorities to improve the management of patients affected by NTM pulmonary disease.

Purpose Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed or used as self-medication in cases of community-acquired pneumonia (CAP). Nevertheless, the consequences of such medication on the risk of pleuroparenchymal complications are not well known. The aim was to investigate whether exposure to NSAIDs prior to hospital admission among patients suffering from CAP is associated with the development of pleural complications or a lung abscess. Methods All consecutive non-immunocompromised patients with CAP and admitted to a university hospital were prospectively included (2-year period). The risk of pleuropulmonary complications was analyzed according to previous exposure to NSAIDs. Results Of the 221 included patients, 40 (18.1%) had developed a pleuropulmonary complication. NSAIDs intake prior to admission was reported for 24 patients (10.9%) who were younger (50.6 ± 18.5 vs. 66.5 ± 16.4 years; p  = 0.001), had less comorbidities (60 vs. 25.1%; p  = 0.001), had a longer duration between the first symptoms of CAP and the start of an antibiotic therapy (6.1 ± 7.6 vs. 2.8 ± 3.8 days; p  = 0.001), and who had a higher incidence of pleuropulmonary complications (33.3 vs. 16.2%; p  = 0.048). In multivariate analyses, two factors were independently associated with the development of pleuroparenchymal complications: NSAIDs intake [Odds Ratio (OR) = 2.57 [1.02–6.64]; p  = 0.049] and alcohol abuse (OR = 2.68 [1.27–5.69]; p  = 0.01). Conclusions Our findings suggest that NSAIDs, often taken by young and healthy patients, may worsen the course of CAP with delayed therapy and a higher rate of pleuropulmonary complications.

The treatment of Mycobacterium avium infections is still long, complex, and often poorly tolerated, besides emergence of resistances. New active molecules that are more effective and better tolerated are deeply needed. Mefloquine and its enantiomers ((+) Erythro-mefloquine ((+)-EMQ) and (-)-Erythro-mefloquine ((-)-EMQ)) have shown efficacy in both in vitro and in vivo , in a mouse model of M . avium intraveinous infection. However, no study reports aerosol model of infection or combination with gold standard treatment. That was the aim of our study. In an aerosol model of M . avium infection in BALB/c mice, we used five treatment groups as followed: Clarithromycin-Ethambutol-Rifampicin (CLR-EMB-RIF, standard of care, n = 15), CLR-EMB-MFQ (n = 15), CLR-EMB-(+)-EMQ (n = 15), CLR-EMB-(-)-EMQ (n = 15) and an untreated group (n = 25). To evaluate drug efficacy, we sacrificed each month over 3 months, 5 mice from each group. Lung homogenates were diluted and plated for colony forming unit count (CFU) expressed in Log10. At each time point, we found a significant difference between the untreated group and each of the treatment groups (p<0.005). The (+)-EMQ-CLR-EMB group was the group with the lowest CFU count at each time point but never reached statistical significance. The results of each group 3 months after treatment are: (+)-EMQ-CLR-EMB (4.43 ± 0.26), RIF-CLR-EMB (4.83 ± 0.37), (-)-EMQ-CLR-EMB (4.82 ± 0.18), MFQ-CLR-EMB (4.70 ± 0.21). In conclusion, MFQ and its enantiomers appear to be as effective as rifampicin in combination therapy. Further studies are needed to evaluate the ability of these drugs to prevent selection of clarithromycin resistant strains and potential for lung sterilization.

Methods We used the Danish National Patient Registry to identify all patients (>15 yr old) with hospitalized CAP in the period 1997-2011, defined as a first-time incident hospital admission with a primary diagnosis of pneumonia, lung abscess, pyothorax, or pleural effusion coded with secondary pneumonia (International Classification of Diseases, 10th revision: [...]even after excluding all patients who redeemed their last NSAID prescription within 10 days before hospital admission, we observed a clear association with pleuropulmonary complications among new NSAID users (Figure 1). Because we also observed a significant association with pleuropulmonary complications in longer-term users, we believe that this association cannot be explained solely by protopathic bias. [...]we found that NSAID use was associated with an increased risk of pleuropulmonary complications in patients hospitalized with CAP.

Background/ObjectivesA growing body of data suggests that obesity influences coronavirus disease 2019 (COVID-19). Our study’s primary objective was to assess the association between body mass index (BMI) categories and critical forms of COVID-19.Subjects/MethodsData on consecutive adult patients hospitalized with laboratory-confirmed COVID-19 at Amiens University Hospital (Amiens, France) were extracted retrospectively. The association between BMI categories and the composite primary endpoint (admission to the intensive care unit or death) was probed in a logistic regression analysis.ResultsIn total, 433 patients were included, and BMI data were available for 329: 20 were underweight (6.1%), 95 have a normal weight (28.9%), 90 were overweight (27.4%), and 124 were obese (37.7%). The BMI category was associated with the primary endpoint in the fully adjusted model; the odds ratio (OR) [95% confidence interval (CI)] for overweight and obesity were respectively 1.58 [0.77–3.24] and 2.58 [1.28–5.31]. The ORs [95% CI] for ICU admission were similar for overweight (3.16 [1.29–8.06]) and obesity (3.05 [1.25–7.82]) in the fully adjusted model. The unadjusted ORs for death were similar in all BMI categories while obesity only was associated with higher risk after adjustment.ConclusionsOur results suggest that overweight (and not only obesity) is associated with ICU admission, but overweight is not associated with death.

Background Ambient air pollution is recognized as a major risk factor for chronic obstructive pulmonary disease (COPD) which is the third leading cause of death worldwide. We examined whether variations in daily outdoor air pollutants levels were associated with excess hospital emergency room visits (ERV) for acute exacerbation of COPD (AECOPD). Methods This two-center ecological cohort study was conducted in Amiens, France. We collected all consecutive ERV for AECOPD throughout 2017 and developed single pollutant models to assess the association between AECOPD and nitrogen dioxide (NO 2 ), ozone (O 3 ), or particulate matter (PM 2.5 and PM 10 ) levels, while adjusting for temperature, hygrometry, influenza circulation and pollen allergy risk. For a subgroup of patients, we also applied geographical modeling to analyze annual exposure to outdoor air pollutants. Results We recorded 240 ERV among 168 COPD patients in 2017 and identified 9 peaks of ERV. There was a statistically significant positive correlation between the daily ERV for AECOPD and the daily average concentrations of PM 2.5 (RR = 1.06 (95%CI = [1.00–1.11]), p  = 0.049), but no correlation with NO 2 , O 3 or PM 10 ( p  = 0.073, p  = 0.114 and p  = 0.119, respectively). Our geographical modeling study revealed that long-term exposure to any of the four outdoor air pollutants was not associated with more frequent AECOPD. Conclusion Even though the pollution levels measured generally remained below or near the 2021 short-term air quality guidelines issued by the World Health Organization, significant aggregate-level associations were found between severe AECOPD leading to ERV and daily concentrations of PM 2.5 . Clinical trial registration NCT03079661.

Background SARS-CoV-2 virus which targets the pulmonary vasculature is supposed to induce an intrapulmonary right to left shunt with an increased pulmonary blood flow. Such vascular injury is difficult to observe because it is hidden by the concomitant lung injury. We report here what may be, to the best of our knowledge, the first case of a pure Covid-19 related Acute Vascular Distress Syndrome (AVDS). Case presentation A 43-year-old physician, tested positive for Covid-19, was addressed to the emergency unit for severe dyspnoea and dizziness. Explorations were non informative with only a doubt regarding a sub-segmental pulmonary embolism (no ground-glass lesions or consolidations related to Covid-19 disease). Dyspnoea persisted despite anticoagulation therapy and normal pulmonary function tests. Contrast-enhanced transthoracic echocardiography was performed which revealed a moderate late right-to-left shunt. Conclusions This case report highlights the crucial importance of the vascular component of the viral disease. The intrapulmonary shunt induced by Covid-19 which remains unrecognized because generally hidden by the concomitant lung injury, can persist for a long time. Contrast-enhanced transthoracic echocardiography is the most appropriate test to propose in case of persistent dyspnoea in Covid-19 patients.

Abstract Rationale Few population-based data are available regarding nontuberculous mycobacteria (NTM) pulmonary disease epidemiology and prognosis. Objectives To examine NTM pulmonary colonization incidence, disease incidence, and prognostic factors. Methods All adults in Denmark with at least one NTM-positive pulmonary specimen during 1997 to 2008 were identified using national medical databases and were categorized as having possible or definite NTM disease or colonization. Measurements and Main Results We calculated annual age-standardized NTM incidence rates and adjusted hazard ratios (HR) of death associated with patient age, sex, comorbidity, NTM species, and NTM disease status. Of 1,282 adults with 2,666 NTM-positive pulmonary specimens, 335 (26%) had definite NTM disease, 238 (19%) possible disease, and 709 (55%) colonization only. NTM incidence rates decreased until 2002, followed by an increase from 2003 to 2008 (mean annual rate per 100,000 person-years: NTM colonization, 1.36; NTM disease, 1.08). Five-year mortality after definite NTM disease was 40.1%. After controlling for potential confounders, 5-year mortality for definite NTM disease was slightly higher than for NTM colonization (adjusted hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.90–1.51). Mycobacterium xenopi was associated with worse prognosis (adjusted HR, 1.51; 95% CI, 0.99–2.33) than the reference Mycobacterium avium complex. High comorbidity level (HR, 2.97), age greater than or equal to 65 years (HR, 9.17), and male sex (female sex HR, 0.73) were predictors of death. Conclusions NTM disease incidence has remained unchanged in Denmark over the past 12 years. Patients with NTM colonization and disease have similarly poor prognosis. Negative prognostic factors include high levels of comorbidity, advanced age, male sex, and M. xenopi.

Introduction Unlike diseases caused by Mycobacterium tuberculosis, M. leprae and M. ulcerans, the epidemiology of pulmonary non-tuberculous mycobacteria (PNTM) has not received due attention in French Guiana. The main objective of the current study was to define the incidence of these PNTM infections: NTM pulmonary diseases (NTM-PD) and casual PNTM isolation (responsible of latent infection or simple colonization). The secondary objectives were to determine species diversity and geographic distribution of these atypical mycobacteria. Methods A retrospective observational study (2008-2018) of French Guiana patients with at least one PNTM positive respiratory sample in culture was conducted. Patients were then classified into two groups: casual PNTM isolation or pulmonary disease (NTM-PD), according to clinical, radiological and microbiological criteria defined by the American Thoracic Society / Infectious Disease Society of America (ATS / IDSA) in 2007. Results 178 patients were included, out of which 147 had casual PNTM isolation and 31 had NTM-PD. Estimated annual incidence rate of respiratory isolates was 6.17 / 100,000 inhabitants per year while that of NTM-PD was 1.07 / 100,000 inhabitants per year. Among the 178 patients, M. avium complex (MAC) was the most frequently isolated pathogen (38%), followed by M. fortuitum then M. abscessus (19% and 6% of cases respectively), the latter two mycobacteria being mainly found in the coastal center region. Concerning NTM-PD, two species were mainly involved: MAC (81%) and M. abscessus (16%). Discussion/Conclusion This is the first study on the epidemiology of PNTM infections in French Guiana. PNTM's incidence looks similar to other contries and metropolitan France and NTM-PD is mostly due to MAC and M.abscessus. Although French Guiana is the French territory with the highest tuberculosis incidence, NTM should not be overlooked.

Abstract Aims To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin–angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. Methods and results All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32–54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61–84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02–2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. Conclusions We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.