Acute Pulmonary Exacerbation Phenotypes in Patients with Cystic Fibrosis.

Rationale: The etiology of cystic fibrosis (CF) pulmonary exacerbations (PEx) is likely multifactorial with viral, bacterial, and non-infectious pathways contributing. Objectives: To determine whether viral infection status and CRP (C-reactive protein) can classify subphenotypes of PEx that differ in outcomes and biomarker profiles. Methods: Patients were recruited at time of admission for a PEx. Nasal swabs and sputum samples were collected and processed using the respiratory panel of the FilmArray multiplex polymerase chain reaction (PCR). Serum and plasma biomarkers were measured. PEx were classified using serum CRP and viral PCR: "pauci-inflammatory" if CRP < 5 mg/L, "non-viral with systemic inflammation" if CRP ⩾ 5 mg/L and no viral infection detected by PCR and "viral with systemic inflammation" if CRP ⩾ 5 mg/L and viral infection detected by PCR. Results: Discovery cohort (n = 59) subphenotype frequencies were 1) pauci-inflammatory (37%); 2) non-viral with systemic inflammation (41%); and 3) viral with systemic inflammation (22%). Immunoglobulin G, immunoglobulin M, interleukin-10, interleukin-13, serum calprotectin, and CRP levels differed across phenotypes. Reduction from baseline in forced expiratory volume in 1 second as percent predicted (FEV1pp) at onset of exacerbation differed between non-viral with systemic inflammation and viral with systemic inflammation (-6.73 ± 1.78 vs. -13.5 ± 2.32%; P = 0.025). Non-viral with systemic inflammation PEx had a trend toward longer duration of intravenous antibiotics versus pauci-inflammation (18.1 ± 1.17 vs. 14.8 ± 1.19 days, P = 0.057). There were no differences in percent with lung function recovery to <10% of baseline FEV1pp. Similar results were seen in local and external validation cohorts comparing a pauci-inflammatory to viral/non-viral inflammatory exacerbation phenotypes. Conclusions: Subphenotypes of CF PEx exist with differences in biomarker profile, clinical presentation, and outcomes.

A Novel Cooling Method and Comparison of Active Rewarming of Mildly Hypothermic Subjects.

OBJECTIVE: To compare the effectiveness of arteriovenous anastomosis (AVA) vs heated intravenous fluid (IVF) rewarming in hypothermic subjects. Additionally, we sought to develop a novel method of hypothermia induction. METHODS: Eight subjects underwent 3 cooling trials each to a core temperature of 34.8±0.6 (32.7 to 36.3°C [mean±SD with range]) by 14°C water immersion for 30 minutes, followed by walking on a treadmill for 5 minutes. Core temperatures (Δtes) and rates of cooling (°C/h) were measured. Participants were then rewarmed by 1) control: shivering only in a sleeping bag; 2) IVF: shivering in sleeping bag and infusion of 2 L normal saline warmed to 42°C at 77 mL/min; and 3) AVA: shivering in sleeping bag and circulation of 45°C warmed fluid through neoprene pads affixed to the palms and soles of the feet. RESULTS: Cold water immersion resulted in a decrease of 0.5±0.5°C Δtes and 1±0.3°C with exercise (P < .01); with an immersion cooling rate of 0.9±0.8°C/h vs 12.6±3.2°C/h with exercise (P < .001). Temperature nadir reached 35.0±0.5°C. There were no significant differences in rewarming rates between the 3 conditions (shivering: 1.3±0.7°C/h, R2 = 0.683; IVF 1.3±0.7°C/h, R2 = 0.863; and AVA 1.4±0.6°C/h, R2 = 0.853; P = .58). Shivering inhibition was greater with AVA but was not significantly different (P = .07). CONCLUSIONS: This study developed a novel and efficient model of hypothermia induction through exercise-induced convective afterdrop. Although there was not a clear benefit in either of the 2 active rewarming methods, AVA rewarming showed a nonsignificant trend toward greater shivering inhibition, which may be optimized by an improved interface.