The 16S rRNA lung microbiome in mechanically ventilated patients: a methodological study.

PURPOSE: Characterization of the respiratory tract bacterial microbiome is in its infancy when compared to the gut microbiota. To limit bias mandates a robust methodology. Specific amplification of the hypervariable (V) region of the 16SrRNA gene is a crucial step. Differences in accuracy exist for one V region to another depending on the sampled environment. We aimed to assess the impact of the primer sequences targeting the V4 region currently used for gut microbiota studies in respiratory samples. Materials and methods: The original 515 F-806R primer pair targets the V4 region of the 16SrRNA gene. We compared two different 515 F-806R primer pairs before Illumina 250 paired-end sequencing for bacterial microbiome analyses of respiratory samples from critically-ill ventilated patients. "S-V4" for "Stringent V4" primer pair is used in two ongoing international projects "the Integrative Human microbiome project (iHMP)" and "the Earth microbiome project (EMP)." "R-V4" for "Relaxed V4" primer pair has been modified to reduce biases against specific environmental taxa. The optimal method was determined by concordance with conventional microbiology. Results: Twenty samples from three patients who developed a ventilator-associated pneumonia (VAP) and four who did not (control ventilated patients) were sequenced. Highly different results were obtained. "S-V4" provided the best agreement with the conventional microbiology for endotracheal aspirate: 89% as compared to 56% for "R-V4." The main difference related to poor Enterobacteriaceae detection with "R-V4" primers. Conclusions: Accuracy of the bacterial lung microbiome composition was highly dependent on the primers used for amplification of the 16 s rRNA hypervariable sequence. This work validates for future lung microbiome studies the use of the 515 F-806R "S-V4" primer pair associated to Illumina® MiSeq paired-end sequencing.

Longer symptom onset to aspiration time predicts success of needle aspiration in primary spontaneous pneumothorax.

BACKGROUND: Needle aspiration (NA) is recommended as first-line treatment of primary spontaneous pneumothorax (PSP). We aimed to assess NA success and the effect of a longer symptom onset to NA time. METHODS: A discovery phase was retrospectively conducted in the intensive care unit of Louis Mourier Hospital (January 2000 to December 2011) followed by a prospective validation cohort (January 2012 to August 2015). The primary outcome was immediate NA success defined by the absence of need for chest tube insertion within 24 hours of the procedure. RESULTS: In the discovery phase, 130 patients were admitted for PSP and 98 had NA as first-line treatment (75%). The immediate success rate of NA was 34.7% and was higher when it was performed ≥48 hours after symptom onset (57.7% vs 25%; p=0.004). In the prospective cohort, 87 patients were admitted for PSP; 71 (82%) had NA as first-step treatment. The immediate success rate was 40.8%. NA was more successful when it was performed after 48 hours of symptoms' onset (34.5% vs 7.1%; p=0.005). A delay between the first symptom and NA procedure ≥48 hours was associated with a higher success of NA (OR=13.54; 95% CI 1.37 to 133). A smaller pneumothorax estimated by Light's index was associated with NA success (OR=0.95; 95% CI 0.92 to 0.98). To what extent some of these pneumothoraces would have had a spontaneous resolution remains unknown. CONCLUSION: When managing PSP with NA, a longer symptom onset to NA time was associated with NA success. TRIAL REGISTRATION NUMBER: NCT02528734.

Outpatient management of primary spontaneous pneumothorax.

The outpatient management of primary spontaneous pneumothorax (PSP) is still debated. The risk of a tension pneumothorax is used to justify active treatment like chest-tube drainage, although outpatient management can reduce both the time in hospital and the cost of treatment. It is also likely to be the patient's choice. This report is a reappraisal of the situations for which outpatient management, by monitoring alone, or using minimally invasive techniques, can be considered.

Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study.

BACKGROUND: Anti-synthetase (AS) and dermato-pulmonary associated with anti-MDA-5 antibodies (aMDA-5) syndromes are near one of the other autoimmune inflammatory myopathies potentially responsible for severe acute interstitial lung disease. We undertook a 13-year retrospective multicenter study in 35 French ICUs in order to describe the clinical presentation and the outcome of patients admitted to the ICU for acute respiratory failure (ARF) revealing AS or aMDA-5 syndromes. RESULTS: From 2005 to 2017, 47 patients (23 males; median age 60 [1st-3rd quartiles 52-69] years, no comorbidity 85%) were admitted to the ICU for ARF revealing AS (n = 28, 60%) or aMDA-5 (n = 19, 40%) syndromes. Muscular, articular and cutaneous manifestations occurred in 11 patients (23%), 14 (30%) and 20 (43%) patients, respectively. Seventeen of them (36%) had no extra-pulmonary manifestations. C-reactive protein was increased (139 [40-208] mg/L), whereas procalcitonine was not (0.30 [0.12-0.56] ng/mL). Proportion of patients with creatine kinase ≥ 2N was 20% (n = 9/47). Forty-two patients (89%) had ARDS, which was severe in 86%, with a rate of 17% (n = 8/47) of extra-corporeal membrane oxygenation requirement. Proportion of patients who received corticosteroids, cyclophosphamide, rituximab, intravenous immunoglobulins and plasma exchange were 100%, 72%, 15%, 21% and 17%, respectively. ICU and hospital mortality rates were 45% (n = 21/47) and 51% (n = 24/47), respectively. Patients with aMDA-5 dermato-pulmonary syndrome had a higher hospital mortality than those with AS syndrome (n = 16/19, 84% vs. n = 8/28, 29%; p = 0.001). CONCLUSIONS: Intensivists should consider inflammatory myopathies as a cause of ARF of unknown origin. Extra-pulmonary manifestations are commonly lacking. Mortality is high, especially in aMDA-5 dermato-pulmonary syndrome.

Acute decompensated pulmonary hypertension.

Acute right heart failure in chronic precapillary pulmonary hypertension is characterised by a rapidly progressive syndrome with systemic congestion resulting from impaired right ventricular filling and/or reduced right ventricular flow output. This clinical picture results from an imbalance between the afterload imposed on the right ventricle and its adaptation capacity. Acute decompensated pulmonary hypertension is associated with a very poor prognosis in the short term. Despite its major impact on survival, its optimal management remains very challenging for specialised centres, without specific recommendations. Identification of trigger factors, optimisation of fluid volume and pharmacological support to improve right ventricular function and perfusion pressure are the main therapeutic areas to consider in order to improve clinical condition. At the same time, specific management of pulmonary hypertension according to the aetiology is mandatory to reduce right ventricular afterload. Over the past decade, the development of extracorporeal life support in refractory right heart failure combined with urgent transplantation has probably contributed to a significant improvement in survival for selected patients. However, there remains a considerable need for further research in this field.