Dana Baran

Overall and peripheral inhomogeneity of ventilation in patients with stable cystic fibrosis

We studied distribution of ventilation in patients with cystic fibrosis (CF) who had not had an exacerbation for some time. Patients performed either the vital capacity nitrogen (N2) single‐breath washout test (VC test) or a modified single‐breath washout consisting of 1 L inspired from functional residual capacity (FRC test) of 90% oxygen (O2), 5% helium (He), and 5% sulfur hexafluoride (SF6). We computed the slopes of phase III of N2 concentration from the VC test (SN2 (VC)) and the phase III slopes of the He (SHe): The SF6 (SSF6), and curves from the FRC test. SN2 (VC) may be regarded as an index of overall ventilation and the difference (SSF6 − SHe) as an index of peripheral ventilation. Three groups were studied: CF, 28 CF patients (8–36 years of age); normal controls (NC), 33 normal nonsmokers (9–55 years of age); and a smoking group (SG), 42 non‐CF smoking patients (39–79 years of age).

Deposition of Nacystelyn from a Dry Powder Inhaler in Healthy Volunteers and Cystic Fibrosis Patients

The aim of this study was to compare, using gamma scintigraphy, the lung deposition of a novel mucoactive agent, Nacystelyn (NAL), administered as a dry powder inhaler (DPI) in six healthy volunteers, six adult patients with cystic fibrosis (CF), and six children and adolescents patients with CF. The correlation between in vitro and in vivo results was also tested. It was first demonstrated that the method of labeling of NAL with 99mTc was reliable as tested by three in vitro methods (multistage liquid impinger, multistage cascade impactor, and 2-stage glass impinger). The deposition of unlabeled NAL, labeled NAL, and the radiolabel was similar in all stages of each device. Furthermore, the fine particle fraction (FPF) was the same on all apparatuses. The mean lung deposition obtained in volunteers was 27.5 ± 13.5%. The results are approximately three times higher than the results obtained previously in healthy volunteers with NAL metered-dose inhalers (MDIs). As expected, the lung deposition observed in patients with CF was lower, e.g., 23.5 ± 7.0% for adults and 16.5 ± 5.9% for children and adolescents. A significant correlation was found between lung deposition and both the patient weight (p < 0.02) and height (p < 0.04). Surprisingly, the peripheral:central (P:C) ratio was similar for the three populations, indicating that the presence of mucus in moderately ill patients with CF does not modify the lung distribution of NAL. The FPF measured in vitro was similar to that obtained in volunteers but higher than that found in both patient populations. The DPI formulation of NAL developed will probably improve patient compliance and comfort in future clinical trials and postmarketing use of the drug.

Structural change of the acinus during growth assessed by single-breath tracer gas washouts

In the present investigation we wanted to study the functional and structural development of the acinus, using a vital capacity (VC) single‐breath tracer gas washout test, modified so that the subject inspired helium (He) and sulfurhexafluoride (SF6) in oxygen. We used as indices of ventilation the slopes of N2 (SN2), He (SHe), and SF6 (SSF6) as well as (SSF6 − SHe), which may be considered an index of acinar mixing linked to acinar structure. We studied two populations: Population I—49 children and adolescents (8–18 years of age); and Population II—18 non‐smoking adults (22–48 years of age). Age and vital capacity (VC) were correlated in Population I, but not in Population II. In both populations there was a significant decrease of SN2, SSF6, and SHe as a function of VC. Growth and VC changes were determinants of these decreases in Population I, while only changes in VC were significant determinants in Population II. For each gas, the regression lines of slope versus VC for Populations I and II were not significantly different; we therefore suggest that the decrease in slope in Population I is mainly due to an increase in lung volume during growth. (SSF6 − SHe) was not correlated with VC in Population I and was negatively correlated with VC in Population II (P < 0.01). This discrepancy implies that a child will have a smaller (SSF6 − SHe) than an adult at comparable VC. Since the magnitude of (SSF6 − SHe) values are related to acinar branching asymmetry, our results suggest that asymmetry of the acinus increases with lung growth and maturation. Pediatr Pulmonol. 1996; 22:230–235.

The Prognostic Implications of Renal Function Recovery and Delayed Graft Function in Kidney Transplantation

Introduction In the general population, lack of renal function recovery (RFR), 90 days after acute kidney injury (AKI) is a contributor to inferior renal outcomes and mortality. Ischemia and reperfusion during kidney transplantation (KT) contributes to AKI and delayed graft function (DGF), a severe form of AKI. Our aim was to analyze the long-term prognostic implications of RFR at 90 days, in recipients with and without DGF. Methods This was a retrospective analysis of adult deceased donor KT recipients (1996 -2016). Outcome of interest was death censored graft failure (DCGF). RFR was calculated using the formula (observed eGFR/predicted eGFR) X 100. Predicted eGFR was half of the donor eGFR plus pre-emptive recipient eGFR, and observed eGFR was the average of 3 best values, 90 days post-KT. Grafts with primary non-function were excluded. The Chronic Kidney Disease Epidemiology Collaboration prediction equation was used to determine the eGFR. Results 941 KT recipients were eligible for analysis, of which 25% had DGF. RFR was divided into 3 tertiles <75% (360), 75-100% (218) and >100% (363). Higher DCGF was noted in recipients that developed DGF, and had RFR<75% (Figure 1). In recipients that developed DGF, RFR had no further prognostic implications on DCGF (Table 1). However, in those that did not develop DGF, RFR<75% was associated with an 82% and 89% higher DCGF in univariate and multivariate analysis, respectively. Figure. No caption available. Table. No title available. Conclusion In recipients that do not develop DGF, 90-day RFR<75% was associated with DCGF. This indicates the prognostic relevance of RFR as a short-term outcome as most KT do not develop DGF. We propose that to truly capture the impact of AKI and ischemia and reperfusion injury during the transplantation surgery, one must quantify RFR over 90 days after KT.

Perioperative Hemoglobin and Delayed Graft Function in Kidney Transplant Recipients

Background A Cochrane review of 31 trials reported no mortality or morbidity advantage with a liberal over restrictive transfusion strategy. Most centers use an absolute hemoglobin concentration (Hb) threshold of 70 g/L for transfusion, unless patients have active cardiac ischemia. However, recent studies have suggested that relative change in hemoglobin levels ([INCREMENT]Hb) is more predictive of patient outcomes. No such analysis has been done in patients undergoing a kidney transplantation, where procured grafts are at high risk of acute tubular necrosis due to ischemia. Given this, we aimed to analyze the relationship between delayed graft function (DGF), and Hb and [INCREMENT]Hb during transplant. Methods We conducted a single-center retrospective chart review of all adult, deceased donor kidney transplants between 2003 and 2017. Recipients of simultaneous multi-organ transplants and those that received a transfusion within the first 24 hours were excluded. Hb was captured at various time points within the first 24 hours post-transplant. [INCREMENT]Hb was defined as = [(pre-transplant Hb – nadir post-transplant Hb)/pre-transplant Hb] x 100. The outcome of interest was DGF, defined as the need for dialysis within the first week post-transplant. We excluded transplants that had primary non-function. Results Of the 934 transplants, 705 were eligible for analysis. Of these 25% (176) experienced DGF. Several baseline differences were noted in those that experienced DGF. Amongst those recipients that developed DGF, Hb values pre-transplant, the lowest Hb post-transplant or [INCREMENT]Hb were not statistically different from those that did not develop DGF (Table 1). In a univariate analysis, only pre-transplant Hb but not the lowest Hb post-transplant or [INCREMENT]Hb were predictive of DGF (Table 2). This effect lost significance in a multivariate analysis. Figure. No caption available. Conclusion In those recipients that did not receive a blood transfusion perioperatively, the relative change in hemoglobin post-transplant was not predictive of DGF. Future work entails analyzing outcomes in those that received a transfusion. Given the risk of sensitization with blood transfusions, our work supports current restrictive transfusion practices in the kidney transplant population.

Lung function in children and adolescents with antecedents of acute rheumatic fever.

Static lung volumes, CO-lung transfer, airway resistance, maximal expiratory flows and lung elastic properties were studied in 29 children and adolescents 1–10 years after recovery from acute rheumatic fever. There were essentially no changes in lung function even in the subjects with a residual valvular disease. The only abnormality was a tendency for the elastic lung recoil at TLC to be low, which is interpreted as probably reflecting a decrease in inspiratory muscle force.