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This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a critical role in restoring homeostasis under pathologic conditions, including infection. Given the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global spread of coronavirus disease 2019 (COVID-19), with subsequent acute respiratory distress syndrome, understanding basic lung physiology in infectious diseases is especially warranted. This review summarizes clinical and preclinical data for GM-CSF in respiratory infections, and the rationale for sargramostim (yeast-derived recombinant human [rhu] GM-CSF) as adjunctive treatment for COVID-19 and other pulmonary infectious diseases.

Determining the optimal timing and progression of mobility exercise has the potential to affect functional recovery of critically ill adults. This study compared standard care with care delivered using a mobility protocol. We examined the effects of exercise on vital signs and inflammatory biomarkers and the effects of the nurse-initiated mobility protocol on outcomes. Prospective, repeated measures study with a control (standard care) and intervention (protocol) period. 75 heterogeneous subjects admitted to a Medical or Surgical intensive care unit (ICU) were enrolled. In <5% of exercise periods, there was a concerning alteration in respiratory rate or peripheral oxygen saturation; no other adverse events occurred. Findings suggested the use of a protocol with one 20minute episode of exercise daily for 2 or more days reduced ICU length of stay. Duration of exercise was linked to increased IL-10, suggesting brief episodes of low intensity exercise positively altered inflammatory dysregulation in this sample. A growing body of evidence demonstrates that early, progressive exercise has significant benefits to intubated adults. These results should encourage clinicians to add mobility protocols to the care of ICU adults and lead to future studies to determine optimal “dosing” of exercise in ICU patients.

Background. The clinical impact of penicillin resistance on the outcome of pneumococcal pneumonia has remained controversial. We performed a meta-analysis of prospective cohort studies to examine the association between penicillin resistance and short-term all-cause mortality for pneumococcal pneumonia. Methods. We retrieved studies published in any language by a comprehensive search of the Medline, Current Contents, and Embase databases for all appropriate articles published up to January 2005. We also manually reviewed bibliographies of retrieved articles, recent national treatment guidelines, and review articles. We included prospective cohort studies that involved adult subjects, and we examined the association between penicillin resistance and short-term mortality for pneumococcal pneumonia. Two reviewers independently extracted data on crude and adjusted risk estimates of all-cause mortality for pneumococcal infections with different levels of penicillin resistance and assessed the methodological quality of selected studies. We also contacted authors to obtain additional information. We performed meta-analyses using a random-effect model. Results. Of 1152 articles identified in the search, 10 studies that involved 3430 patients (most of whom were hospitalized) were included. The mortality rate was 19.4% in the penicillin-nonsusceptible Streptococcus pneumoniae group and 15.7% in the penicillin-susceptible S. pneumoniae group. The combined relative risks of all-cause mortality for the penicillin-nonsusceptible, -intermediate, and -resistant S. pneumoniae groups, compared with the penicillin-susceptible S. pneumoniae group, were 1.31 (95% confidence interval [CI], 1.08–1.59), 1.34 (95% CI, 1.13–1.60), and 1.29 (95% CI, 1.01–1.66), respectively. The combined adjusted relative risks of mortality for penicillin-nonsusceptible versus penicillin-susceptible S. pneumoniae group was 1.29 (95% CI, 1.04–1.59) for the 6 studies that adjusted for age, comorbidities, and severity of illness. There was minimal between-study heterogeneity in these analyses. Conclusion. Penicillin resistance is associated with a higher mortality rate than is penicillin susceptibility in hospitalized patients with pneumococcal pneumonia. Additional efforts are needed to understand the mechanisms of this association.

ICU-acquired paresis (ICUAP) is common in survivors of critical illness. There is significant associated morbidity, including prolonged time on the ventilator and longer hospital stay. However, it is unclear whether ICUAP is independently associated with mortality, as sicker patients are more prone and existing studies have not adjusted for this. To test the hypothesis that ICUAP is independently associated with increased mortality. Secondarily, to determine if handgrip dynamometry is a concise measure of global strength and is independently associated with mortality. A prospective multicenter cohort study was conducted in intensive care units (ICU) of five academic medical centers. Adults requiring at least 5 days of mechanical ventilation without evidence of preexisting neuromuscular disease were followed until awakening and were then examined for strength. We measured global strength and handgrip dynamometry. The primary outcome was in-hospital mortality and secondary outcomes were hospital and ICU-free days, ICU readmission, and recurrent respiratory failure. Subjects with ICUAP (average MRC score of < 4) had longer hospital stays and required mechanical ventilation longer. Handgrip strength was lower in subjects with ICUAP and had good test performance for diagnosing ICUAP. After adjustment for severity of illness, ICUAP was independently associated with hospital mortality (odds ratio [OR], 7.8; 95% confidence interval [CI], 2.4-25.3; P = 0.001). Separately, handgrip strength was independently associated with hospital mortality (OR, 4.5; 95% CI, 1.5-13.6; P = 0.007). ICUAP is independently associated with increased hospital mortality. Handgrip strength is also independently associated with poor hospital outcome and may serve as a simple test to identify ICUAP. Clinical trial registered with www.clinicaltrials.gov (NCT00106665).

Abstract INTRODUCTION Recommendations regarding ventilation strategies in the setting of COVID-19, which may culminate in a clinical picture similar to ARDS, have not yet been well established. Prone positioning has shown benefit as an adjunct supportive measure for patients who develop ARDS. However, studies assessing the benefit of prone positioning have excluded patients with reduced intracranial compliance resulting in a unique predicament, whereby patients with concomitant neurological diagnoses and ARDS have no defined treatment algorithm or recommendations for management. METHODS A systematic review of the literature, performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2009 guidelines, yielded 10 articles for analysis. Utilizing consensus from these articles, in combination with review of multi-institutional proning protocols for patients with non-neurologic conditions, a proning protocol for patients with intracranial pathology and concomitant ARDS was developed. RESULTS Among the 10 studies included in final analysis, there was consensus that prone positioning should be considered when there is evidence of acute lung injury or ARDS in patients with neurologic injury. Patients may be proned with a speciality bed or manually on a standard bed with the assistance of seven to nine personnel, in the manner described herein. Special consideration for patients requiring frequent neurologic exams and patients at risk of cardiac arrest or seizure are discussed. CONCLUSION While elevations in ICP and reductions in CPP do occur during proning, they may not occur to a degree that would warrant exclusion of prone ventilation as a treatment modality for patients with ARDS and concomitant neurological diagnoses. In cases where ICP, CPP, and PbtO2 can be monitored, prone-position ventilation should be considered a safe and viable therapy.