Baclofen destabilises breathing during sleep in healthy humans: A randomised, controlled, double-blind crossover trial.

AIMS: Periodic breathing is frequent in patients with severe heart failure. Apart from being an indicator of severity, periodic breathing has its own deleterious consequences (sleep-related oxygen desaturations, sleep fragmentation), which justifies attempts to correct it irrespective of the underlying disease. Animal models and human data suggest that baclofen can reconfigure respiratory central pattern generators. We hypothesised that baclofen, a GABAB agonist, may thus be able to correct periodic breathing in humans. METHODS: Healthy volunteers were exposed to hypoxia during sleep. Participants who developed periodic breathing (n = 14 [53 screened]) were randomly assigned to double-blind oral baclofen (progressively increased to 60 mg/d) or placebo. The primary outcome was the coefficient of variation (CoVar) of respiratory cycle total time considered as an indicator of breathing irregularity. Secondary outcomes included the CoVar of tidal volume, apnoea-hypopnoea index, sleep fragmentation index and ventilatory complexity (noise limit). RESULTS: The analysis was conducted in 9 subjects after exclusion of incomplete datasets. CoVar of respiratory cycle total time significantly increased with baclofen during non-rapid eye movement sleep (median with placebo 56.00% [37.63-78.95]; baclofen 85.42% [68.37-86.40], P = .020; significant difference during the N1-N2 phases of sleep but not during the N3 phase). CoVar of tidal volume significantly increased during N1-N2 sleep. The apnoea-hypopnoea index, sleep fragmentation index and ventilatory complexity were not significantly different between placebo and baclofen. CONCLUSION: Baclofen did not stabilise breathing in our model. On the contrary, it increased respiratory variability. Baclofen should probably not be used in patients with or at risk of periodic breathing.

Bacterial coinfection in critically ill COVID-19 patients with severe pneumonia.

Severe 2019 novel coronavirus infectious disease (COVID-19) with pneumonia is associated with high rates of admission to the intensive care unit (ICU). Bacterial coinfection has been reported to be rare. We aimed at describing the rate of bacterial coinfection in critically ill adult patients with severe COVID-19 pneumonia. All the patients with laboratory-confirmed severe COVID-19 pneumonia admitted to the ICU of Tenon University-teaching hospital, from February 22 to May 7th, 2020 were included. Respiratory tract specimens were obtained within the first 48 h of ICU admission. During the study period, 101 patients were referred to the ICU for COVID-19 with severe pneumonia. Most patients (n = 83; 82.2%) were intubated and mechanically ventilated on ICU admission. Overall, 20 (19.8%) respiratory tract specimens obtained within the first 48 h. Staphylococcus aureus was the main pathogen identified, accounting for almost half of the early-onset bacterial etiologies. We found a high prevalence of early-onset bacterial coinfection during severe COVID-19 pneumonia, with a high proportion of S. aureus. Our data support the current WHO guidelines for the management of severe COVID-19 patients, in whom antibiotic therapy directed to respiratory pathogens is recommended.

Severe COVID-19 with acute respiratory distress syndrome (ARDS) in a sickle cell disease adult patient: case report.

BACKGROUND: Sickle-cell anaemia is a widespread genetic disease prevalent worldwide among African and African-American populations. The pathogenesis is most often revealed by pulmonary conditions, including acute thoracic syndrome, which is affecting the life expectancy of these populations. The global spread of CoV2-SARS infection with a respiratory tropism, endothelial damages and procoagulant status endangers the SCD population. However, with only a few case reports, consequences of the Covid-19 pandemic on SCD population remain poorly known. CASE PRESENTATION: We report a case of a 33-year-old man with a history of homozygous SS homozygous sickle cell anemia who consulted on March 24, 2020 for febrile dyspnea 11 days after the onset of symptoms. A nasopharyngeal swab was positive for SARS-CoV-2. His respiratory status worsened rapidly in the emergency room and then in ICU leading to severe ARDS requiring intubation, curarization, and venovenous ECMO. Hematologically, severe hemolysis associated with major thrombocytopenia without documented spinal cord injury was noted. Several transfusion exchanges are performed. The evolution was finally slowly favorable and led to discharge from the intensive care unit and then from the hospital. CONCLUSIONS: This case recalls the importance of an increased prevention policy against COVID-19among the SCD population. In addition, from a therapeutic point of view, it advocates (1) a high preventive anticoagulation from the outset according to the level of D-dimers (2) the use of venovenous ECMO in this particular case, whereas this technique has had rather disappointing results in acute chest syndromes. (3) Unexpectedly, our patient did not develop pulmonary arterial hypertension (PAH) and acute cor pulmonale (ACP), whereas this is a common feature of ARDS during SCD. These last two observations suggest a different pathophysiology of pulmonary disorders in SCD patients in the case of SARS COv2. It could be associated with marked hypoxemia secondary to pulmonary vascular vasodilation.

Severe hemoptysis in post-tuberculosis bronchiectasis precipitated by SARS-CoV-2 infection.

BACKGROUND: Since the beginning of SARS-CoV-2 outbreak in China, severe acute respiratory syndrome has been widely descripted. Hemoptysis has rarely been observed in SARS-CoV-2 infection. We report here a case of severe hemoptysis in post-tuberculosis bronchiectasis precipitated by SARS-CoV-2 infection and managed in a referral center. CASE PRESENTATION: A 58-year-old man was admitted to our intensive care unit for severe hemoptysis with history of post-tuberculosis bronchiectasis. At ICU admission the patient had fever and severe acute respiratory failure requiring high flow oxygen therapy. Respiratory tract sampling was positive for SARS-CoV-2. Multi-detector computed tomography angiography pointed out localized bronchiectasis on the left lower lobe and enlarged left bronchial and phrenic arteries; bronchial arteriography with distal embolization was performed with favorable outcome and no bleeding recurrence. CONCLUSIONS: To our knowledge, this is the first case of acute exacerbation of bronchiectasis related to SARS-CoV-2 infection and complicated by severe hemoptysis. Whether the virus may play a role in the dysregulation of airway haemostasis, and contribute to episodes of hemoptysis in patients with chronic pulmonary diseases and predisposing factors might be investigated.

Desquamative interstitial pneumonia induced by metal exposure. A case report and literature review.

BACKGROUND: Forms of interstitial pneumonia secondary to exposure to an air-contaminant are varied and so far, insufficiently described. OBJECTIVES/METHODS: We report here a case of a 57-year-old patient managed in our department for the exploration of MRC grade 2 dyspnoea and interstitial pneumonia. He mentioned multiple occupational and domestic exposures such as hens' excrements, asbestos and metal particles; he also had a previous history of smoking. RESULTS: High-resolution computed tomography showed ground glass opacities predominating in posterior territories and surrounding cystic lesions or emphysematous destruction. The entire etiological assessment revealed only macrophagic alveolitis with giant multinucleated cells on the bronchoalveolar lavage. A surgical lung biopsy allowed us to refine the diagnosis with evidence of desquamative interstitial pneumonia and pulmonary granulomatosis. Finally, the analysis of the mineral particles in the biopsy revealed abnormally high rates of Zirconium and Aluminium. We were therefore able to conclude to a desquamative interstitial pneumonia associated with pulmonary granulomatosis linked to metal exposure (Aluminium and Zirconium). The clinical, functional and radiological evolution was favorable after a systemic corticosteroid treatment with progressive decay over one year. CONCLUSION: This presentation reports the first case to our knowledge of desquamative interstitial pneumonitis related to exposure to Zirconium and the third one in the context of Aluminium exposure. The detailed analysis of the mineral particles present on the surgical lung biopsy allows for the identification of the relevant particle to refine the etiological diagnosis, to guide the therapeutic management and to give access to recognition as an occupational disease. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 79-84).

Acute bronchodilation increases ventilatory complexity during resting breathing in stable COPD: toward mathematical biomarkers of ventilatory function?

Human tidal breathing features mathematical complexity and breath-by-breath variability. Fluctuations in these descriptors from one state to another are related to the load imposed on the respiratory system. We hypothetized that bronchodilators would increase ventilatory complexity and variability in patients suffering from chronic obstructive pulmonary disease (COPD). Eleven patients with stable COPD (9 men; age 48-79; FEV1 42-80%; FRC above 120%) were studied before and after 400 µg salbutamol. Breath-by-breath variability (coefficient of variation of tidal volume and breathing frequency -f) and ventilatory complexity (noise limit - NL, a quantifier of nonlinearity and complexity; largest Lyapunov exponent - LLE, an indicator of the sensitivity of the system to initial conditions) were described. Acute bronchodilation revealed or increased nonlinearity (NL 31% [20-38] to 43% [35-58], P=0.0051). Little changes in variability were observed (increased coefficient of variation of f). These observations might open new avenues toward resting breathing pulmonary function testing and novel respiratory biomarkers suitable for home-based lung disease monitoring.