Insights into the Treatment of SBD With Imaging Richard J. Schwab, - PDF document

Insights into the Treatment of SBD With Imaging Richard J. Schwab, M.D. Professor of Medicine Interim Chief, Division of Sleep Medicine Medical Director, Penn Sleep Centers University of Pennsylvania Perelman School of Medicine Insights into the Treatment of SBD With Imaging - Disclosures • NIH grants - PPG (phenotyping and OSA) • ResMed Grant/Registry to study OSA/CSA and CPAP in hospitalized patients • Jazz clinical trial for daytime sleepiness in OSA • Inspire CT study to examine upper airway anatomy with hypoglossal nerve stimulation 1

Insights into the Treatment of SBD with Upper Airway Imaging • Treatment of sleep apnea – Weight loss – CPAP – Oral appliances • Mandibular repositioning devices • Upper airway surgery – Transoral robotic surgery (TORS) – Hypoglossal nerve stimulation Weight Loss and Sleep Apnea • How much weight loss results in clinical improvement? – Weight loss of 5 - 10% may be effective • Does size of parapharyngeal fat pads and tongue (tongue fat) decrease with weight loss? • Does size of lateral pharyngeal walls, soft palate decrease with weight loss? – Weight loss is associated with reductions in both fat (75%) and fat-free mass (25%) 2

Demographic Comparison between OSA and Control Patients after 6 Months of Weight Loss Weight Stable * Weight Loss * All Participants Variable p † p † p † Control OSA Control OSA Control OSA N 18 51 – 3 8 – 14 38 – Age (years) 40.4 ± 13.6 49.6 ± 10.6 0.0151 30.3 ± 10.1 51.5 ± 10.1 0.0244 42.3 ± 14.1 48.6 ± 11.2 0.1467 Male 16.67% 41.18% 0.0605 66.67% 50.00% >0.999 7.14% 39.47% 0.0251 White 47.06% 46.00% 0.9397 100.00% 37.50% 0.1818 38.46% 48.65% 0.5261 Height (inches) 65.9 ± 2.8 67.0 ± 4.2 0.2436 67.0 ± 5.3 68.0 ± 4.8 0.6082 66.0 ± 2.2 66.9 ± 4.1 0.2877 Weight (pounds) Baseline 226 ± 50.4 271 ± 54.0 0.0033 232 ± 28.6 303 ± 64.3 0.0412 228 ± 55.0 266 ± 52.5 0.0340 Follow-up 206 ± 36.5 241 ± 50.8 0.0029 230 ± 28.9 301 ± 62.2 0.0412 202 ± 37.8 225 ± 38.1 0.0690 Change -20.41 ± 26.85 -29.94 ± 32.76 0.2307 -2.60 ± 3.65 -1.42 ± 4.72 0.5403 -26.05 ± 27.98 -41.82 ± 29.08 0.0871 Percent Change -7.98 ± 8.33 -10.50 ± 10.59 0.3115 -1.14 ± 1.64 -0.40 ± 1.37 0.4142 -10.22 ± 8.06 -14.78 ± 8.52 0.0874 * Weight Stable defined as <2.5% weight change, and weight loss as >2.5% decrease in weight; † p-value from T-test (parametric) or Kruskal-Wallis (non-parametric) test for continuous measures and chi-square or Fisher’s exact test for categorical measures. 26 pound weight loss (10%) in controls and a 42 pound weight loss (15%) in apneics Demographic Comparison between OSA and Control Patients after 6 Months of Weight Loss All Participants Weight Stable * Weight Loss * Variable p † p † p † Control OSA Control OSA Control OSA BMI (kg/m 2 ) Baseline 36.6 ± 7.8 42.4 ± 7.5 0.0095 37.3 ± 10.6 46.1 ± 8.2 0.2207 36.7 ± 7.8 41.8 ± 7.5 0.0447 Follow-up 33.3 ± 5.9 37.8 ± 7.3 0.0128 36.8 ± 10.3 45.9 ± 8.0 0.1530 32.5 ± 5.0 35.3 ± 5.4 0.0925 Change -3.26 ± 4.20 -4.64 ± 5.13 0.2675 -0.45 ± 0.58 -0.21 ± 0.64 0.5403 -4.17 ± 4.35 -6.53 ± 4.49 0.0989 Percent Change -7.98 ± 8.33 -10.50 ± 10.59 0.3115 -1.14 ± 1.64 -0.40 ± 1.37 0.4142 -10.22 ± 8.06 -14.78 ± 8.52 0.0874 AHI (events/hour) Baseline 4.7 ± 3.2 39.5 ± 27.7 <0.0001 7.1 ± 1.8 43.9 ± 34.3 0.0143 3.9 ± 3.1 39.5 ± 27.4 <0.0001 Follow-up 6.4 ± 7.1 21.8 ± 20.8 <0.0001 12.1 ± 6.7 37.4 ± 20.8 0.0244 5.2 ± 7.1 16.3 ± 19.1 0.0039 Change 1.66 ± 5.83 -18.20 ± 23.41 <0.0001 5.00 ± 4.96 -6.47 ± 28.22 0.3074 1.33 ± 5.97 -23.69 ± 20.28 <0.0001 61.32 ± Percent Change 99.38 ± 221.2 -40.39 ± 60.43 0.0165 8.41 ± 55.41 0.2207 117.6 ± 247.6 -63.44 ± 29.31 0.0171 54.61 * Weight Stable defined as <2.5% weight change, and weight loss as >2.5% decrease in weight; † p-value from T-test (parametric) or Kruskal-Wallis (non-parametric) test for continuous measures and chi-square or Fisher’s exact test for categorical measures. No significant changes in AHI in controls or apneics in the weight stable groups. In the weight loss groups no significant change in AHI in controls but in apniecs AHI reduced significantly by 24 events/hour 3

Percent Changes in Airway Size within and between Controls and Apneics after 6 Months of Weight Loss Controls All Participants Controls OSA Cases vs. OSA Airway Measures p † p † p † p ‡ N mean ± SD N mean ± SD N mean ± SD RP Airway Volume (mm 3 ) 51 15.35 ± 45.21 0.0190 14 17.38 ± 46.07 0.1815 37 14.58 ± 45.49 0.0590 0.8459 RP Cross Sectional Area (mm 2 ) 51 21.64 ± 45.12 0.0012 14 22.42 ± 46.39 0.0937 37 21.35 ± 45.28 0.0069 0.9404 RP Minimum Area (mm) 47 49.12 ± 110.3 0.0038 12 40.12 ± 76.7 0.0972 35 52.20 ± 120.6 0.0150 0.7473 RP Minimum AP Distance (mm) 46 6.34 ± 37.72 0.2605 12 9.69 ± 31.22 0.3053 34 5.15 ± 40.12 0.4591 0.7245 RP Minimum Lateral Distance 46 13.93 ± 33.26 0.0067 12 16.33 ± 33.14 0.1159 34 13.09 ± 33.76 0.0305 0.7754 RG Airway Volume (mm 3 ) 51 6.65 ± 33.65 0.1643 14 14.73 ± 31.96 0.1082 37 3.59 ± 34.19 0.5268 0.2961 RG Cross Sectional Area (mm 2 ) 51 4.91 ± 26.05 0.1846 14 11.36 ± 22.12 0.0769 37 2.47 ± 27.27 0.5856 0.2812 RG Minimum Area (mm) 46 6.79 ± 41.07 0.2680 12 24.07 ± 59.05 0.1856 34 0.69 ± 31.48 0.8984 0.2133 RG Minimum AP Distance (mm) 45 -1.39 ± 28.15 0.7421 12 -3.17 ± 26.64 0.6883 33 -0.74 ± 29.05 0.8842 0.8016 RG Minimum Lateral Distance 45 7.82 ± 40.29 0.1994 12 21.05 ± 51.02 0.1808 33 3.01 ± 35.32 0.6272 0.1873 † p-value from paired T-test examining significance of within group change; ‡ p-value from T-test comparing changes between OSA and controls Weight loss resulted in significant increases in the percent changes in Retropalatal cross sectional area and minimum area in apneics but not controls. No change in RG region Percent Changes in Soft Tissues within and between Controls and Apneics after 6 Months of Weight Loss Controls All Participants Controls OSA Cases vs. OSA Soft Tissue Measures p † p † p † p ‡ N mean ± SD N mean ± SD N mean ± SD Total Soft Tissue (mm 3 ) 51 -6.90 ± 7.39 <0.0001 14 -3.48 ± 5.05 0.0230 37 -8.20 ± 7.77 <0.0001 0.0404 Soft Palate (mm 3 ) 51 -1.62 ± 16.67 0.4898 14 -1.85 ± 10.86 0.5346 37 -1.54 ± 18.53 0.6168 0.9409 Genioglossus (mm 3 ) 51 -4.65 ± 9.22 0.0007 14 -1.96 ± 8.57 0.4071 37 -5.66 ± 9.37 0.0008 0.2044 Tongue Fat (mm 3 ) 51 -19.71 ± 16.35 <0.0001 14 -13.17 ± 18.73 0.0207 37 -22.19 ± 14.89 <0.0001 0.0788 Tongue Volume (mm 3 ) 51 -4.83 ± 8.68 0.0002 14 -1.43 ± 6.29 0.4102 37 -6.11 ± 9.17 0.0003 0.0855 Fat Pads (mm 3 ) 51 -29.17 ± 14.85 <0.0001 14 -27.48 ± 16.45 <0.0001 37 -29.81 ± 14.39 <0.0001 0.6226 Pterygoid (mm 3 ) 51 -11.77 ± 13.30 <0.0001 14 -10.15 ± 12.06 0.0077 37 -12.38 ± 13.84 <0.0001 0.5973 RP Lateral Walls (mm 3 ) 51 -11.61 ± 16.06 <0.0001 14 -6.83 ± 18.41 0.1882 37 -13.41 ± 14.95 <0.0001 0.1946 RG Lateral Walls (mm 3 ) 51 -1.85 ± 18.76 0.4858 14 4.46 ± 19.19 0.4007 37 -4.23 ± 18.30 0.1683 0.1418 Total Lateral Walls (mm 3 ) 51 -8.24 ± 11.86 <0.0001 14 -2.61 ± 14.30 0.5071 37 -10.37 ± 10.23 <0.0001 0.0357 † p-value from paired T-test examining significance of within group change; ‡ p-value from T-test comparing changes between OSA and controls Significant reductions in the volumes of the tongue, fat pads, pterygoids, lateral walls, total soft tissue and tongue fat (but not soft palate) in apneics with weight loss 4

Normal Pre Weight-Loss Apneic Pre Weight-Loss Normal Post Weight-Loss Apneic Post Weight-Loss Correlations between Percent Change in AHI and Percent Change in Soft Tissues among OSA Cases Adjusted Model † Unadjusted Airway Measure N rho p N rho p Weight (pounds) 50 0.68 <.0001 49 0.67 <.0001 Total Soft Tissue (mm 3 ) 49 0.25 0.0799 48 0.21 0.1565 Soft Palate (mm 3 ) 49 -0.10 0.4942 48 -0.12 0.4517 Genioglossus (mm 3 ) 49 0.17 0.2373 48 0.13 0.4022 Tongue Fat (mm 3 ) 49 0.63 <.0001 48 0.62 <.0001 Total Tongue Volume (mm 3 ) 49 0.18 0.2257 48 0.17 0.2523 Fat Pads (mm 3 ) 49 0.28 0.0531 48 0.20 0.1973 RP Lateral Walls (mm 3 ) 49 0.41 0.0038 48 0.39 0.0083 RG Lateral Walls (mm 3 ) 49 0.06 0.6864 48 -0.01 0.9633 Total Lateral Walls (mm 3 ) 49 0.35 0.0147 48 0.29 0.0501 † Partial correlation adjusted for age, gender, and race; ‡ Partial correlation adjusted for age, gender, race, baseline weight and percent change in weight. Significant correlations between reductions in tongue fat and the RP lateral walls and reductions in AHI in apneics with weight loss 5

CPAP - Airway 3D Volumes RP RP RG RG 0 cm H 2 0 5 cm H 2 0 10 cm H 2 0 15 cm H 2 0 Schwab et al, AJRCCM 154:1106-1116, 1996 CPAP - 0 cm H 2 0 CPAP - 15 cm H 2 0 Schwab et al, AJRCCM 154:1106-1116, 1996 6

0 cm H 2 0 5 cm H 2 0 CPAP Settings 10 cm H 2 0 15 cm H 2 0 Schwab et al, AJRCCM 154:1106-1116, 1996 Mid-sagittal MRI with and without CPAP in a Normal Subject 15 cm H 2 0 0 cm H 2 0 (Schwab et al, AJRCCM 154:1106-1116, 1996) 7