Background: Cystic fibrosis (CF) is a genetic disease affecting multiple organ systems of the body and is characterized by mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Previous work has shown that a single dose of aβ-agonist increases cardiac output (Q) and stroke volume (SV) and decreases systemic vascular resistance (SVR) in healthy subjects. This effect is attenuated in patients with CF; however, the mechanism is unknown. Potential explanations for this decreased cardiovascular response to a β-agonist in CF include inherent cardiovascular deficits secondary to the CFTR mutation, receptor desensitization from prolonged β-agonist use as part of clinical care, or inhibited drug delivery to the bloodstream due to mucus buildup in the lungs. This study sought to determine the effects of endogenous epinephrine (EPI) and norepinephrine (NE) on cardiovascular function in CF and to evaluate the relationship between cardiovascular function and CFTR F508del mutation. Methods: A total of 19 patients with CF and 31 healthy control subjects completed an assessment of Q (C 2 H 2 rebreathing), SV (calculated from Q and heart rate [HR]), Q and SV indexed to body surface area (BSA, QI, and SVI, respectively), SVR (through assessment of Q and mean arterial blood pressure [MAP]), and HR (from 12-lead electrocardiogram [ECG]) at rest along with plasma measures of EPI and NE. We compared subjects by variables of cardiovascular function relative to EPI and NE, and also based on genetic variants of the F508del mutation (homozygous deletion for F508del, heterozygous deletion for F508del, or no deletion of F508del). Results: Cystic fibrosis patients demonstrated significantly lower BSA (CF = 1.71 ± 0.05 m 2 vs healthy = 1.84 ± 0.04 m 2 , P = .03) and SVI (CF = 30.6 ± 2.5 mL/beat/m 2 vs healthy = 39.9 ± 2.5 mL/beat/m 2 , P = .02) when compared with healthy subjects. Cystic fibrosis patients also demonstrated lower Q (CF = 4.58 ± 0.36 L/min vs healthy = 5.71 ± 0.32 L/min, P = .03) and SV (CF = 54 ± 5.5 mL/beat vs healthy = 73.3 ± 4.5 mL/beat, P = .01), and a higher HR (CF = 93.2 ± 3.9 bpm vs healthy = 80.5 ± 2.7 bpm, P < .01) and SVR (CF = 2082 ± 156 dynes*s/cm −5 vs healthy = 1616 ± 74 dynes*s/cm −5 , P = .01) compared with healthy subjects. Furthermore, CF patients demonstrated a lower SV ( P < .01) corrected for NE when compared with healthy subjects. No significant differences were seen in HR or Q relative to NE, or SVR relative to EPI. Differences were seen in SV (F (2,14) = 7.982, ...

Haemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder that is accompanied by a high mortality rate when the underlying aetiology is miliary tuberculosis. We report a case of tuberculosis (TB)-associated HLH in a haemodialysis patient, from a TB-endemic region, who missed two sessions of dialysis before developing the primary symptoms of HLH. The patient presented with non-specific findings including pancytopenia, coagulopathy and transaminitis. Computer-tomography imaging and microbiology from bronchoalveolar lavage evidenced miliary tuberculosis. Further testing revealed the TB-associated-HLH characteristic pattern of thrombocytosis, leukopenia, transaminitis, hyperferritinemia and elevated fibrinogen. The patient initially demonstrated improvement after initiation of anti-TB therapy. However, soon thereafter began to paradoxically deteriorate and then expire from apparent tuberculosis-immune reconstitution inflammatory syndrome. This case highlights the importance of early diagnosis and treatment, and consequently of the utility of diagnostic systems such as the HScore in cases of high clinical suspicion.

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) lead to altered ion regulation, resulting in CF. CFTR also plays an important role in cardiac function. We have shown that β‐agonist inhalation results in increased cardiac output (Q), stroke volume (SV), and decreased systemic vascular resistance (SVR) in healthy humans, suggesting stimulation of the β‐adrenergic receptors via inhalation. We have also shown that this cardiovascular (CV) response is attenuated in CF, which could be due to receptor desensitization or inhibited drug delivery to the blood stream due to mucus build‐up. This study sought to determine the effects of epinephrine (EPI) and norepinephrine (NE) on CV function in CF. 11 CF patients and 27 controls completed a cycle ergometery test with measures of Q, SV, SVR, and HR along with EPI and NE. CF patients had lower Q corrected for NE at 50% and peak exercise (rest: Q/NE= 0.012 ±0.002 vs 0.017 ±0.002; 50%: Q/NE= 0.026 ±0.004 vs 0.045 ±0.004; peak: Q/NE= 0.03 ±0.004 vs 0.05 ±0.005, CF vs healthy, p<0.05) and lower SV corrected for NE at rest, 50%, and peak (rest: SV/NE= 0.12 ±0.03 vs 0.22 ±0.02; 50%: SV/NE= 0.17 ±0.04 vs 0.32 ±0.03; peak: SV/NE= 0.18 ±0.04 vs 0.35 ±0.03, CF vs healthy, p<0.05), no difference in SVR when corrected for EPI (rest: SVR/EPI= 53 ±13 vs 33 ±4; 50%: SVR/EPI= 28 ±7 vs 15 ±2; peak: SVR/EPI= 22 ±5 vs 15 ±3; in CF vs healthy). These results suggest that CF patients have lower cardiac function relative to circulating NE, no difference in SVR relative to EPI, indicating impairment in cardiac function, likely as a result from a loss of CFTR function.