Correction to: 33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018).

After publication of this supplement [1, 2], it was brought to our attention that due to an error authors were missing in the following abstracts. This has now been included in this correction.

Impact of particle size and aerosolization time on the metabolic effect of an inhaled insulin aerosol.

The effects were compared of varying aerosol particle size and aerosolization time within each breath on the metabolic effect elicited by inhalation of a liquid insulin aerosol in comparison with that after subcutaneous injection (s.c.) of regular insulin. In this single-center, open-label euglycemic glucose clamp study, 13 healthy non-smoking subjects received five administrations of insulin in randomized order on separate study days, once by s.c. (0.15 U/kg of regular insulin) and four times by inhalation. Subjects inhaled 1.5 U/kg of liquid insulin aerosol administered by the Aerodose Insulin Inhaler (Aerogen Inc., Mountain View, CA) configured to deliver two aerosol particle sizes--fine [F, 4.4 +/- 0.3 microm (mean +/- SD)] or very fine (VF, 3.5 +/- 0.2 microm)--and two aerosolization times (aerosol released for the first 2 or 4 s after the start of each 5-s inhalation). Glucose infusion rate (GIR) values necessary to keep blood glucose concentrations constant at 5.0 mmol/L were determined over a 6-h period following insulin administration. After inhalation of insulin, the onset of action was substantially more rapid on all four inhalation study days than after s.c. insulin, and the time to maximal action [t(GIRmax) (min)] was reached earlier: F/2 s, 127 +/- 54; F/4 s, 128 +/- 55; VF/2 s, 158 +/- 91; VF/4 s, 132 +/- 72; s.c., 175 +/- 69 (P < 0.0001). The longer aerosolization time (4 vs. 2 s) resulted in higher maximal metabolic action [GIR(max) (mg/kg/min), F/4 s 8.1 +/- 3.6, VF/4 s 8.4 +/- 2.7 vs. F/2 s 6.6 +/- 2.4, VF/2 s 7.2 +/- 2.4 (P = 0.01 for 4 s vs. 2 s, grouped data)], total metabolic activity [area under the curve of GIR 0-6 h (g/kg), F/4 s 1.97 +/- 0.92, VF/4 s 2.14 +/- 0.86 vs. F/2 s 1.56 +/- 0.68, VF/2 s 1.78 +/- 0.60 (P = 0.01)], and relative biopotency [F/4 s 10.6 +/- 4.0%, VF/4 s 11.7% +/- 4.1% vs. F/2 s 8.5 +/- 3.2%, VF/2 s 9.7 +/- 2.4% (P = 0.01)]. None of these summary measures was significantly affected by particle size. No drug- or device-related adverse events were observed. This study shows that aerosolization time, but not particle size, in the ranges studied, had an impact on the metabolic effect elicited by inhaled insulin, allowing rational selection of delivery parameters for further clinical testing. Based on the observed biopotency and the rapid onset of action, inhalation of a liquid insulin aerosol generated by the Aerodose Insulin Inhaler shows promise for covering prandial insulin requirements.

Dose-response relationships of inhaled insulin delivered via the Aerodose insulin inhaler and subcutaneously injected insulin in patients with type 2 diabetes.

OBJECTIVE: To compare the dose-response relationship following inhalation of regular insulin delivered via the Aerodose insulin inhaler with that following subcutaneously injected regular insulin in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Twenty-four patients with type 2 diabetes (21 nonsmoking men, aged 36-80 years) each received two of three doses of 80, 160, or 240 units inhaled regular insulin, delivered via a clinical Aerodose insulin inhaler, and two of three corresponding doses of 8, 16, or 24 units by subcutaneous injection under isoglycemic clamp conditions on 4 separate study days in an incomplete block design study. Glucose infusion rates (GIRs) and serum insulin concentrations were monitored over the following 8 h. RESULTS: Inhaled insulin exhibited significantly shorter time-to-peak insulin levels (T(max) 77 +/- 66 vs. 193 +/- 104 min, P < 0.001) and time-to-peak metabolic effects (T(GIRmax) 240 +/- 94 vs. 353 +/- 60 min, P < 0.001) compared with subcutaneously injected insulin. Comparison of total insulin absorption (insulin area under the curve [AUC]) versus total metabolic effect (GIR-AUC) from 0 to 8 h (group means) revealed overlapping dose-response relationships for both inhaled and subcutaneous injection treatments. Comparison of slopes revealed no significant differences between the inhaled and subcutaneous injection treatment groups (P = 0.6). No significant differences in either relative bioavailability or relative biopotency were found among doses, indicating a consistent subcutaneous injection-to-inhaled dosing conversion ratio among doses. No serious adverse events or clinically relevant changes in lung function were observed. CONCLUSIONS: The overlapping dose-response curves of inhaled and subcutaneous treatments together with a consistent relative bioavailability and relative biopotency for inhaled insulin across doses suggest that the Aerodose insulin inhaler will deliver a pharmacologically predictable insulin dose to patients with diabetes similar to that observed following subcutaneous injection.

Absorption and metabolic effect of inhaled insulin: intrapatient variability after inhalation via the Aerodose insulin inhaler in patients with type 2 diabetes.

OBJECTIVE: To compare the intrapatient variability of the pharmacokinetic and pharmacodynamic responses to inhaled regular insulin (INH) delivered via the Aerodose Insulin Inhaler with that of subcutaneously injected regular insulin (SC) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 15 patients with type 2 diabetes (nonsmokers, 10 men, aged 47-77 years) received two 240-unit doses of INH, delivered via a clinical Aerodose Insulin Inhaler and two 24-unit doses of SC under euglycemic clamp conditions on four separate study days. Glucose infusion rates (GIRs) and serum insulin concentrations were monitored over the following 8 h. Comparisons of intrapatient coefficients of variation (CV) were used to assess the reproducibility of INH versus SC. RESULTS: INH showed a bioavailability (0-8 h postdosing) of 16% and biopotency of 13% relative to SC. Comparison of the CVs (%) for area under the curve for serum insulin and GIR between INH and SC showed no significant differences between the treatments during 0-3 h (19% for INH versus 23% for SC) or 0-8 h (22% for INH versus 16% for SC). INH exhibited a shorter time to peak insulin concentration (T(max) [mean +/- SD] 76 +/- 51 vs. 193 +/- 66 min) and shorter time to peak metabolic effect (T(GIRmax) 170 +/- 53 vs. 244 +/- 75 min) compared with SC (P < 0.001). No adverse events were observed. CONCLUSIONS: Comparable dosing reproducibility and shorter time to peak action of INH compared with SC suggest that INH delivered via the Aerodose Insulin Inhaler can provide reliable preprandial dosing of insulin in patients with type 2 diabetes.