Pure SARS-CoV-2 related AVDS (Acute Vascular Distress Syndrome).

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.

In vivo probe-based confocal laser endomicroscopy in chronic interstitial lung diseases: Specific descriptors and correlation with chest CT.

BACKGROUND AND OBJECTIVE: Probe-based confocal laser endomicroscopy (pCLE) enables in vivo microimaging of the distal lung, during bronchoscopy. This study aims at identifying pCLE descriptors of chronic interstitial lung diseases (ILD), their correlations with chest HRCT and assessing inter-observer agreement. METHODS: pCLE was performed in 21 healthy volunteers (HV) and 59 non-smoking ILD patients, including 19 patients with idiopathic pulmonary fibrosis (IPF) or asbestosis, 15 with connective tissue disease-associated ILD (CTD-ILD), 17 with sarcoidosis and 8 with hypersensitivity pneumonitis (HP). pCLE descriptors were identified in ILD on the basis of comparison with HV. RESULTS: Nine pCLE descriptors were more frequent in ILD compared to HV, with good inter-observer agreement, including fluorescent bronchiolar cells (sarcoidosis, CTD-ILD and HP), fluorescent alveolar cells (CTD-ILD and HP), small alveolar entrance rings (IPF or asbestosis and CTD-ILD), enlarged axial elastic fibres (IPF or asbestosis), septal fibres (IPF or asbestosis, CTD-ILD and HP), disorganized acinar network and rigid acinar network (IPF or asbestosis and CTD-ILD), dense elastic network (IPF or asbestosis) and alveolar fluorescent nodular structures (in sarcoidosis) (P < 0.01, Fisher's exact test, all comparisons). The distribution of nodules on computed tomography (CT) appeared to correlate with pCLE alveolar nodular structures, rigid acinar network and septal fibres, while reticulations were associated with septal fibres and disorganized or dense acinar network; ground-glass opacities on CT with small alveolar entrances, rigid elastic network and septal fibres; and honeycombing with septal fibres. CONCLUSION: In the four groups of ILD studied, 9 pCLE descriptors are described, which appear specific and reproducible, and correlate with chest HRCT patterns.

Cost-effectiveness of lung volume reduction coil treatment in patients with severe emphysema: results from the 2-year follow-up crossover REVOLENS study (REVOLENS-2 study).

BACKGROUND: The REVOLENS study compared lung volume reduction coil treatment to usual care in patients with severe emphysema at 1 year, resulting in improved quality-adjusted life-year (QALY) and higher costs. Durability of the coil treatment benefit and its cost-effectiveness at 2 years are now assessed. METHODS: After one year, the REVOLENS trial's usual care group patients received coil treatment (second-line coil treatment group). Costs and QALYs were assessed in both arms at 2 years and an incremental cost-effectiveness ratio in cost per QALY gained was calculated. The uncertainty of the results was estimated by probabilistic bootstrapping. RESULTS: The average cost of coil treatment in both groups was estimated at €24,356. The average total cost at 2 years was €9655 higher in the first-line coil treatment group (p = 0.07) and the difference in QALY between the two groups was 0.127 (p = 0.12) in favor of first-line coil treatment group. The 2-year incremental cost-effectiveness ratio (ICER) was €75,978 / QALY. The scatter plot of the probabilistic bootstrapping had 92% of the replications in the top right-hand quadrant. CONCLUSION: First-line coil treatment was more expensive but also more effective than second-line coil treatment at 2 years, with a 2-year ICER of €75,978 / QALY. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01822795 .

Treatment of Other Nontuberculous Mycobacteria.

Nontuberculous mycobacteria (NTM) are numerous, and for the vast majority of them, randomized studies are lacking and data regarding optimal treatment are limited. When Mycobacterium avium complex (MAC) and M. abscessus are excluded, the main NTM are M. xenopi, M. kansasii, M. malmoense, M. szulgai, and M. simiae. Treatment is long (at least 12 months after culture conversion according to recommendations by scientific societies) and difficult (at least three drugs are required, each of which have potential adverse events). Moreover, optimal treatment is unknown for the vast majority of NTM and efficacy of treatment is not 100%. That is why, balance between benefit and risk is fundamental. For M. xenopi, the second most common NTM isolated in Europe, treatment is classically based on macrolides or fluoroquinolones, associated with ethambutol and rifampicin. For M. kansasii, the cornerstone of treatment is rifampicin, which should be associated with two other drugs: ethambutol plus isoniazid or clarithromycin. M. malmoense, which is common in Northern Europe, can be treated by rifampicin, ethambutol, and clarithromycin and/or fluoroquinolones.

Prospective Observational Study on the Association Between Serum Mannose-Binding Lectin Levels and Severe Outcome in Critically Ill Patients with Pandemic Influenza Type A (H1N1) Infection.

BACKGROUND: Mannose-binding lectin (MBL) plays an important role in the innate immune response. In addition to activating the complement, MBL can induce cytokine production and contribute to a deleterious inflammatory response with severe A(H1N1)pdm09 virus infection. Our aim was to determine if serum MBL levels correlate with the risk of mortality in intensive care units (ICU) patients with A(H1N1)pdm09 infection. METHODS: Prospective observational study was performed in ICU patients with acute respiratory distress syndrome due to influenza A(H1N1)pdm09 virus. Demographic characteristics and severity indices were recorded at ICU admission. MBL was assayed from blood drawn at influenza diagnosis within 24-48 h following the ICU admission. Outcomes were compared according to MBL levels. Results are expressed as median and interquartile range. RESULTS: Serum MBL levels were studied in 27 patients (age: 56 [IQR 29] years) with severe A(H1N1)pdm09 infection and in 70 healthy controls. Median admission SAPSII and SOFA scores were 49 [IQR 26] and 12 [IQR 5], respectively. Mortality rate after a 30-day was 37%. MBL was significantly higher in non-survivors (3741 [IQR 2336] ng/ml) vs survivors (215 [IQR 1307] ng/ml), p = 0.006, as well as control group (1814 [IQR 2250] ng/ml), p = 0.01. In contrast, MBL levels in survivors group were significantly lower than the controls group (215 [IQR 1307] ng/ml vs. 1814 [IQR 2250] ng/ml, p = 0.005). MBL cut-off > 1870 ng/ml had a sensitivity of 80% and a specificity of 88.2% for mortality [AUC = 0.82 (95% CI 0.63-0.94)]. Kaplan-Meier analysis demonstrated a strong association between MBL levels and mortality (log-rank 7.8, p = 0.005). MBL > 1870 ng/ml was independently associated with mortality (HR = 8.7, 95% CI 1.2-29.1, p = 0.007). CONCLUSIONS: This study shows that baseline MBL > 1870 ng/ml is associated with higher mortality in ICU patients with severe A(H1N1)pdm09 infection.

Home Environment as a Source of Life-Threatening Azole-Resistant Aspergillus fumigatus in Immunocompromised Patients.

A case of fatal aspergillosis due to a TR46/Y121F/T289A azole-resistant Aspergillus fumigatus is reported. Environmental investigations at the patient's residence led to the recovery of TR46/Y121F/T289A isolates, genotypically indistinguishable from the clinical isolate, supporting for the first time the direct role of household as potential source of azole-resistant invasive aspergillosis.

Non-steroidal Anti-inflammatory Drugs may Worsen the Course of Community-Acquired Pneumonia: A Cohort Study.

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.

Lung Volume Reduction Coil Treatment vs Usual Care in Patients With Severe Emphysema: The REVOLENS Randomized Clinical Trial.

IMPORTANCE: Therapeutic options for severe emphysema are limited. Lung volume reduction using nitinol coils is a bronchoscopic intervention inducing regional parenchymal volume reduction and restoring lung recoil. OBJECTIVE: To evaluate the efficacy, safety, cost, and cost-effectiveness of nitinol coils in treatment of severe emphysema. DESIGN, SETTING, AND PARTICIPANTS: Multicenter 1:1 randomized superiority trial comparing coils with usual care at 10 university hospitals in France. Enrollment of patients with emphysema occurred from March to October 2013, with 12-month follow-up (last follow-up, December 2014). INTERVENTIONS: Patients randomized to usual care (n = 50) received rehabilitation and bronchodilators with or without inhaled corticosteroids and oxygen; those randomized to bilateral coil treatment (n = 50) received usual care plus additional therapy in which approximately 10 coils per lobe were placed in 2 bilateral lobes in 2 procedures. MAIN OUTCOMES AND MEASURES: The primary outcome was improvement of at least 54 m in the 6-minute walk test at 6 months (1-sided hypothesis test). Secondary outcomes included changes at 6 and 12 months in the 6-minute walk test, lung function, quality of life as assessed by St George's Respiratory Questionnaire (range, 0-100; 0 being the best and 100 being the worst quality of life; minimal clinically important difference, ≥4), morbidity, mortality, total cost, and cost-effectiveness. RESULTS: Among 100 patients, 71 men and 29 women (mean age, 62 years) were included. At 6 months, improvement of at least 54 m was observed in 18 patients (36%) in the coil group and 9 patients (18%) in the usual care group, for a between-group difference of 18% (1-sided 95% CI, 4% to ∞; P = .03). Mean between-group differences at 6 and 12 months in the coil and usual care groups were +0.09 L (95% CI, 0.05 L to ∞) (P = .001) and +0.08 L (95% CI, 0.03 L to ∞) (P = .002) for forced expiratory volume in the first second, +21 m (95% CI, -4 m to ∞) (P = .06) and +21 m (95% CI, -5 m to ∞) (P = .12) for 6-minute walk distance, and -13.4 points (95% CI, -8 points to ∞) and -10.6 points (95% CI, -5.8 points to ∞) for St George's Respiratory Questionnaire (1-sided P < .001 for both). Within 12 months, 4 deaths occurred in the coil group and 3 in the usual care group. The mean total 1-year per-patient cost difference between groups was $47,908 (95% CI, $47,879-$48,073) (P < .001); the incremental cost-effectiveness ratio was $782,598 per additional quality-adjusted life-year. CONCLUSIONS AND RELEVANCE: In this preliminary study of patients with severe emphysema followed up for 6 months, bronchoscopic treatment with nitinol coils compared with usual care resulted in improved exercise capacity with high short-term costs. Further investigation is needed to assess durability of benefit and long-term cost implications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01822795.

Lung cancer screening by low-dose CT scan in France: final results of the DEP KP80 study after three rounds.

BACKGROUND: In prior randomised controlled trials, lung cancer screening using low-dose computed tomography (LDCT) has been shown to reduce lung cancer mortality and overall mortality. Despite these results, organised screening in France remains a challenge. This study assessed the feasibility and efficacy of lung cancer screening within a real-life context in a French administrative territory. METHODS: DEP KP80 was a single-arm prospective study. Participants aged between 55 and 74 years, smokers or former smokers of ≥30 pack-years, were recruited. An annual LDCT scan was scheduled and three rounds were performed. Subjects were selected by general practitioners or pulmonologists, who checked the inclusion criteria and prescribed the CT scan. FINDINGS: Between March 2016 and February 2020, 1254 participants were enrolled. Overall, 945 (75.4%) participants underwent baseline LDCT (T0), 376 (42.8%) completed the first round (T1) and 270 (31%) the second (T2) one. Forty-two lung cancers were diagnosed, 30 cancers (71.4%) were stage I or II and 34 cancers (80.9%) were treated surgically. In this study, the overall positive predictive value for a positive screening was 48% (95% CI 37-59) and the negative predictive value 100% (95% CI 100-100). INTERPRETATION: This study demonstrated the feasibility and efficacy of lung cancer screening in a real-life context with most lung cancers diagnosed at an early stage and surgically removed. Our results also highlighted the importance of participation in each round, underlining the fact that optimising organisation is a major goal. FUNDING: Agence Régionale de Santé de Picardie, La Ligue contre le cancer, le Conseil Départemental de la Somme, and AstraZeneca.

In vivo probe-based confocal laser endomicroscopy in amiodarone-related pneumonia.

Probe-based confocal laser endomicroscopy (pCLE) allows microscopic imaging of the alveoli during bronchoscopy. The objective of the study was to assess the diagnostic accuracy of pCLE for amiodarone-related pneumonia (AMR-IP). Alveolar pCLE was performed in 36 nonsmoking patients, including 33 consecutive patients with acute or subacute interstitial lung disease (ILD), of which 17 were undergoing treatment with amiodarone, and three were amiodarone-treated patients without ILD. Nine out of 17 patients were diagnosed with high-probability AMR-IP (HP-AMR-IP) by four experts, and three separate observers. Bronchoalveolar lavage findings did not differ between HP-AMR-IP and low-probability AMR-IP (LP-AMR-IP) patients. In HP-AMR-IP patients, pCLE showed large (>20 µm) and strongly fluorescent cells in 32 out of 38 alveolar areas. In contrast, these cells were observed in only two out of 39 areas from LP-AMR-IP patients, in one out of 59 areas from ILD patients not receiving amiodarone and in none of the 10 areas from amiodarone-treated patients without ILD (p<0.001; HP-AMR-IP versus other groups). The presence of at least one alveolar area with large and fluorescent cells had a sensitivity, specificity, negative predictive value and positive predictive value for the diagnosis of AMR-IP of 100%, 88%, 100% and 90%, respectively. In conclusion, pCLE appears to be a valuable tool for the in vivo diagnosis of AMR-IP in subacute ILD patients.

Behavior of general physicians about lung cancer screening in a French region hosting a pilot study.

INTRODUCTION: Lung cancer is the leading cause of cancer-related death in France and has a 5-year survival rate of 20%. Recent prospective randomized controlled trials revealed that lung cancer-specific mortality decreased in patients who underwent screening using low-dose chest computed tomography (low-dose CT). The DEP KP80 pilot study conducted in 2016 showed that an organized lung cancer screening campaign involving general practitioners was feasible. MATERIAL AND METHOD: We conducted a descriptive observational study of screening practices by sending a self-reported questionnaire to 1013 general practitioners practicing in the Hauts-de-France region. Our study's primary aim was to investigate the knowledge and practices of general practitioners in the Hauts-de-France region of France regarding lung cancer screening using low-dose CT. The secondary endpoint was to compare practices between general practitioners in the Somme department who had experience of experimental screening and their colleagues in the rest of the region. RESULTS: The response rate was 18.8% (190 completed questionnaires). Even though 69.5% of the physicians were unaware of the potential benefits of organized low-dose CT screening for lung cancer, 76% proposed screening tests for individual patients. Despite its proven ineffectiveness, chest radiography was still the most widely recommended screening modality. Half of the physicians stated that they had already prescribed chest CT to screen for lung cancer. Additionally, only 36.3% proposed chest CT screening for patients aged over 50 years with a history of more than 30 pack-years. The physicians working in the Somme department (61% had participated in the DEP KP80 pilot study) were more aware of low-dose CT as a screening modality, and offered it significantly more than their colleagues in the other departments (61.1% vs 13.4% p<0.01). All the physicians were in favor of an organized screening program. CONCLUSION: More than a third of general practitioners in the Hauts-de-France region offered for lung cancer screening using chest CT, although only 18% specified low-dose CT. Before an organized screening program can be set up, good practice guidelines must be made available about lung cancer screening.