Effect of Airway Calibre on Sensitivity to Rostral Fluid Shift in Asthma

Swati A. Bhatawadekar 1 ;  Gabriel Keller 2 ;  Cristina Francisco 1;  Mark D. Inman 3 ;  Jeffrey J. Fredberg 4 ;  Susan Tarlo 5 ;  Owen D. Lyons 5 ;  Azadeh Yadollahi 1, 5

1. UHN-Toronto Rehabilitation Institute; 2. Universidade Federal do Rio de Janeiro; 3. McMaster University; 4. Harvard T.H Chan School of Public Health; 5. University of Toronto

Introduction: Excessive lower (intrathoracic) airways narrowing and worse breathing symptoms, particularly during the night is common in asthma, and thought to result from circadian variations in airway inflammation, recumbent position, and sleep. However, the exact mechanism remains unknown. Despite optimized treatments, asthmatics still report nighttime asthma symptoms and poor sleep suggesting that other factors may contribute. We recently showed that in asthmatic subjects, upon moving from the upright to supine position, as during sleep, fluid retained in the legs moves out of the legs and accumulates in the thorax (rostral fluid shift) causing swelling of the airway wall, narrowing airway lumen, and increasing lower airway narrowing (J Appl Physiol (1985). 2017 Jan 12:jap.00969.2016). In this study, we hypothesized that narrow baseline caliber of lower airways amplifies the effects of rostral fluid shift on lower airway narrowing in asthma.

Methods: Healthy subjects and individuals with a clinical diagnosis of asthma lay supine for 30 min. During supine, they received lower body positive pressure (LBPP from 10 to 30min) to reproduce fluid shift out of the legs similar to the amount of fluid shift overnight. At 0 min and 30 min in the supine position, respiratory resistance at 5 Hz (R5) was measured with impulse oscillometry, and leg and thoracic fluid volumes (LFV, TFV) with bioelectrical impedance. Sensitivity to fluid shift was defined as the change in R5 per change in the TFV from 0 min to 30 min (?R5/?TFV). Sensitivity between the two groups was compared using t-test and correlation was assessed by linear regression and Spearman analysis.

Results:  In 18 healthy subjects (age: 51.9 ± 10.5 yrs, FEV1/FVC Z-score: -0.4±1.1) and 15 asthmatics (58.5±9.8 yrs, -2.1±1.3), the increases in the TFV with LBPP were similar (p>0.05). ?R5/?TFV was larger in the asthmatics than in the healthy subjects (p=0.007), and correlated with baseline R5 in the supine position (?=0.7, p = 0.005). No such association was observed in the healthy subjects (p=0.6). In the asthmatics, the increases in R5-R20 (normalized to baseline R5-R20) were larger than the increases in R20 normalized by baseline R20 (28.3 ± 16.5% vs. 9.2 ± 9.8%, paired t-test, p = 0.0005).

Discussion: Our results suggest that asthma patients with higher baseline R5 such as those with severe asthma, asthmatic women, and obese individuals may be at higher risk of lower airway narrowing due to overnight rostral fluid shift. These results have important clinical implications to i) examine the effects of overnight rostral fluid shift on lower airway narrowing and asthma symptoms in individuals with narrower lower airways ii) develop treatments to reduce day time fluid accumulation and  subsequent nocturnal fluid shift to the thorax in these patients.