Contribution of rostral fluid shift to intrathoracic airway narrowing in asthma

Abstract

In asthma, supine posture and sleep increase intrathoracic airway narrowing. When humans are supine, because of gravity fluid moves out of the legs and accumulates in the thorax. We hypothesized that fluid shifting out of the legs into the thorax contributes to the intrathoracic airway narrowing in asthma. Healthy and asthmatic subjects sat for 30 min and then lay supine for 30 min. To simulate overnight fluid shift, supine subjects were randomized to receive increased fluid shift out of the legs with lower body positive pressure (LBPP, 10-30 min) or none (control) and crossed over. With forced oscillation at 5 Hz, respiratory resistance (R5) and reactance (X5, reflecting respiratory stiffness) and with bioelectrical impedance, leg and thoracic fluid volumes (LFV, TFV) were measured while subjects were seated and supine (0 min, 30 min). In 17 healthy subjects (age: 51.8 ± 10.9 yr, FEV/FVC score: -0.4 ± 1.1), changes in R5 and X5 were similar in both study arms ( > 0.05). In 15 asthmatic subjects (58.5 ± 9.8 yr, -2.1 ± 1.3), R5 and X5 increased in both arms (ΔR5: 0.6 ± 0.9 vs. 1.4 ± 0.8 cmHO·l·s, ΔX5: 0.3 ± 0.7 vs. 1.1 ± 0.9 cmHO·l·s). The increases in R5 and X5 were 2.3 and 3.7 times larger with LBPP than control, however ( = 0.008, = 0.006). The main predictor of increases in R5 with LBPP was increases in TFV (r = 0.73, = 0.002). In asthmatic subjects, the magnitude of increases in X5 with LBPP was comparable to that with posture change from sitting to supine (1.1 ± 0.9 vs. 1.4 ± 0.9 cmHO·l·s, = 0.32). We conclude that in asthmatic subjects fluid shifting from the legs to the thorax while supine contributed to increases in the respiratory resistance and stiffness. In supine asthmatic subjects, application of positive pressure to the lower body caused appreciable increases in respiratory system resistance and stiffness. Moreover, these changes in respiratory mechanics correlated positively with increase in thoracic fluid volume. These findings suggest that fluid shifts from the lower body to the thorax may contribute to overnight intrathoracic airway narrowing and worsening of asthma symptoms.

Reduced Baseline Airway Caliber Relates to Larger Airway Sensitivity to Rostral Fluid Shift in Asthma

“…Since there is a strong inverse relationship between airway diameter and airway resistance (West, 2008 ), it may be expected that these differences in airway response to rostral fluid shifts between healthy and asthmatic subjects may be related to the differences in baseline airway caliber. Indeed, in our recent study (Bhatawadekar et al, 2017 ), as well as in other studies (Duggan et al, 2004 ; Cavalcanti et al, 2006 ), asthmatic subjects had greater respiratory resistance and stiffness than did healthy subjects at baseline in both upright and supine positions, thus implying differences in the baseline airway caliber. Therefore, it may be concluded that for similar amount of fluid accumulation in the lower airways walls, airways with a smaller lumen will have more narrowing and consequently more pronounced increase in their resistance compared to airways with a larger lumen.…”

“…On changing to the supine position as during sleep, the fluid is reabsorbed rapidly from the interstitial space to the intravascular space of the legs (Thompson et al, 1928 ; Fawcett and Wynn, 1960 ), and redistributed to the upper body, including to the thorax and neck. We refer here to this process as a rostral fluid shift (Bhatawadekar et al, 2017 ). Evidence suggests that in asthma, nocturnal rostral fluid shift to the thorax during sleep may play a role in the pathogenesis of overnight airway narrowing in asthma.…”

“…However, this did not occur in healthy subjects and in asthmatic subjects without nocturnal worsening. In our recent study (Bhatawadekar et al, 2017 ), we used lower body positive pressure (LBPP) to simulate overnight rostral fluid shift from the legs to the upper body as occurs during sleep (Redolfi et al, 2009 ). In that study, we found that thoracic fluid volume increased significantly with LBPP, and for similar amounts of fluid accumulation in the thorax, asthmatic subjects experienced a greater increase in the resistance and stiffness of the respiratory system than do healthy subjects.…”

Effects of physical exercise training on nocturnal symptoms in asthma: Systematic review

“…Although, the included studies did not evaluate overnight changes in lung function, it is unlikely that exercise training will cause overnight changes if it did not change daytime lung function. Another factor that may be associated with the nocturnal worsening of asthma is the overnight rostral fluid shift from the legs to the thorax which can increase fluid accumulation in the lower airway wall, narrow airway lumen, and worsen asthma symptoms [ 25 , 26 ]. Previous studies in patients with sleep apnea have shown that physical training during the day can reduce overnight fluid shift out of the legs and improve sleep apnea severity [ 89 ] and snoring [ 90 ].…”

“…During sleep, recumbent posture causes a reduction in the lung volumes, respiratory muscle tone, and lung compliance [ 22 – 24 ]. Moreover, recumbent posture also causes a shift of fluid from the legs to the thorax (rostral fluid shift) that is associated with airway narrowing in asthma [ 25 , 26 ]. In addition, during sleep there is an overnight decrease in plasma cortisol and an increase in airway inflammation, which in turn increases cholinergic tone [ 16 , 17 ], and enhances airway hyper-responsiveness.…”