Rationale: The identification of informative elements of the host response to infection may improve the diagnosis and management of bacterial pneumonia.Objectives: To determine whether the absence of alveolar neutrophilia can exclude bacterial pneumonia in critically ill patients with suspected infection and to test whether signatures of bacterial pneumonia can be identified in the alveolar macrophage transcriptome.Methods: We determined the test characteristics of alveolar neutrophilia for the diagnosis of bacterial pneumonia in three cohorts of mechanically ventilated patients. In one cohort, we also isolated macrophages from alveolar lavage fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages.Measurements and Main Results: An alveolar neutrophil percentage less than 50% had a negative predictive value of greater than 90% for bacterial pneumonia in both the retrospective (n = 851) and validation cohorts (n = 76 and n = 79). A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to alveolar neutrophilia.
Conclusions:The absence of alveolar neutrophilia has a high negative predictive value for bacterial pneumonia in critically ill patients with suspected infection. Macrophages can be isolated from alveolar lavage fluid obtained during routine care and used for RNA-Seq analysis. This novel approach may facilitate a longitudinal and multidimensional assessment of the host response to bacterial pneumonia.
The presence of a normal lung microbiome and the interaction of that microbiome with other microbiota have an important but previously overlooked impact on the pathogenesis of HAP/VAP. Deep sequencing suggests that the repertoire of microorganisms and the pattern of bacterial communities associated with HAP/VAP remains incompletely understood but recent studies are adding greater clarity.
Background: WHO Group 1 pulmonary arterial hypertension (PAH) is a progressive and potentially fatal disease. Individuals living at higher altitude are exposed to lower barometric pressure and hypobaric hypoxemia. This may result in pulmonary vasoconstriction and contribute to disease progression. We sought to examine the relationship between living at moderately high altitude and PAH characteristics. Methods: Forty-two US centers participating in the Pulmonary Hypertension Association Registry (PHAR) enrolled patients who met the definition of WHO Group 1 PAH. We utilized baseline data and patient questionnaire responses. Patients were divided into two groups: moderately high altitude residence (home >4,000 ft) and low altitude residence (home <4,000 ft) based on zip-code. Clinical characteristics, hemodynamic data, patient demographics and patient reported quality of life metrics were compared. Results: Controlling for potential confounders (age, sex at birth, body mass index (BMI), supplemental oxygen use, race, 100-day cigarette use, alcohol use, and PAH medication use), subjects residing at moderately high altitude had a 6-minute walk distance (6MWD) 32 meters greater than those at low altitude, despite having a pulmonary vascular resistance (PVR) that was 2.2 Wood units (WU) higher. Additionally, those residing at moderately high altitude had 3.7 times greater odds of using supplemental oxygen. Conclusion: Patients with PAH who live at moderately high altitude have a higher PVR and are more likely to need supplemental oxygen. Despite these findings, moderately high altitude PHAR patients have better functional tolerance as measured by 6MWD. It is possible that a âhigh-altitude phenotypeâ of PAH may exist. These findings warrant further study.
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