A pilot study to assess the effects of preventing fluid retention in the legs by wearing compression stockings on overnight airway narrowing in mild asthma.

PURPOSE: Nocturnal asthma is a sign of asthma worsening and could be partially due to more fluid drawn into the thorax during sleep by gravitational force and/or pharyngeal collapse in those with obstructive sleep apnea. Wearing compression stockings during the day reduces fluid shift from the legs to the neck overnight. However, the potential effect of wearing compression stockings to reduce fluid accumulation in the leg and to improve nocturnal small airway narrowing in patients with asthma has not been investigated. This study investigates whether reducing leg fluid volume by wearing compression stockings during the day would attenuate small airway narrowing in patients with asthma before and after sleep. METHODS: We enrolled 11 participants with asthma. All participants underwent overnight polysomnography with or without wearing compression stockings for 2 weeks. Before and after sleep, leg fluid volume (LFV) was measured by bioelectrical impedance, and airway narrowing was primarily assessed by respiratory system resistance and reactance at 5 Hz (R5 and X5 respectively) using oscillometry. RESULTS: After 2 weeks of wearing compression stockings, the LFV measured in the evening was reduced (∆ = - 192.6 ± 248.3 ml, p = 0.02), and R5 and X5 improved (∆ = - 0.7 ± 0.9 cmH2O/L/s, p = 0.03 and 0.2 ± 1.4 cmH2O/L/s, p = 0.05 respectively). No changes were observed in the morning. CONCLUSIONS: Preventing fluid retention in the legs by wearing compression stockings for 2 weeks during the day, reduced LFV and airway narrowing in the evening in all participants with asthma, but not in the morning after sleep.

Positive expiratory pressure: a potential therapy to mitigate acute bronchoconstriction in the asthma of obesity.

Late-onset nonallergic (LONA) asthma in obesity is characterized by increased peripheral airway closure secondary to abnormally collapsible airways. We hypothesized that positive expiratory pressure (PEP) would mitigate the tendency to airway closure during bronchoconstriction, potentially serving as rescue therapy for LONA asthma of obesity. The PC20 [provocative concentration of methacholine causing 20% drop in forced expiratory volume in 1 s (FEV1)] dose of methacholine was determined in 18 obese participants with LONA asthma. At each of four subsequent visits, we used oscillometry to measure input respiratory impedance (Zrs) over 8 min; participants received their PC20 concentration of methacholine aerosol during the first 4.5 min. PEP combinations of either 0 or 10 cmH2O either during and/or after the methacholine delivery were applied, randomized between visits. Parameters characterizing respiratory system mechanics were extracted from the Zrs spectra. In 18 patients with LONA asthma [14 females, body mass index (BMI): 39.6 ± 3.4 kg/m2], 10 cmH2O PEP during methacholine reduced elevations in the central airway resistance, peripheral airway resistance, and elastance, and breathing frequency was also reduced. During the 3.5 min following methacholine delivery, PEP of 10 cmH2O reduced Ax and peripheral elastance compared with no PEP. PEP mitigates the onset of airway narrowing brought on by methacholine challenge and airway closure once it is established. PEP thus might serve as a nonpharmacological therapy to manage acute airway narrowing for obese LONA asthma.NEW & NOTEWORTHY Standard pharmacological treatments are not effective in people with obesity and asthma. We assessed the efficacy of positive expiratory pressure (PEP) as a therapy to mitigate airway hyperresponsiveness in the asthma of obesity. Our results indicate that PEP might serve as a nonpharmacological therapy to manage acute airway narrowing in obese individuals with late-onset nonallergic asthma.

Central airway collapse is related to obesity independent of asthma phenotype.

BACKGROUND AND OBJECTIVE: Late-onset non-allergic asthma in obesity is characterized by an abnormally compliant, collapsible lung periphery; it is not known whether this abnormality exists in proximal airways. We sought to compare collapsibility of central airways between lean and obese individuals with and without asthma. METHODS: A cross-sectional study comparing luminal area and shape (circularity) of the trachea, left mainstem bronchus, right bronchus intermedius and right inferior lobar bronchus at RV and TLC by CT was conducted. RESULTS: In 11 lean controls (BMI: 22.4 (21.5, 23.8) kg/m2 ), 10 lean individuals with asthma (23.6 (22.0, 24.8) kg/m2 ), 10 obese controls (45.5 (40.3, 48.5) kg/m2 ) and 21 obese individuals with asthma (39.2 (35.8, 42.9) kg/m2 ), lumen area and circularity increased significantly with an increase in lung volume from RV to TLC for all four airways (P < 0.05 for all). Changes in area and circularity with lung volume were similar in obese individuals with and without asthma, and both obese groups had severe airway collapse at RV. In multivariate analysis, change in lumen area was related to BMI and change in circularity to waist circumference, but neither was related to asthma diagnosis. CONCLUSION: Excessive collapse of the central airways is related to obesity, and occurs in both obese controls and obese asthma. Increased airway collapse could contribute to ventilation abnormalities in obese individuals particularly at lower lung volumes, and complicate asthma in obese individuals.

Contribution of rostral fluid shift to intrathoracic airway narrowing in asthma.

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, FEV1/FVC z score: -0.4 ± 1.1), changes in R5 and X5 were similar in both study arms (P > 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 cmH2O·l-1·s-1, ΔX5: 0.3 ± 0.7 vs. 1.1 ± 0.9 cmH2O·l-1·s-1). The increases in R5 and X5 were 2.3 and 3.7 times larger with LBPP than control, however (P = 0.008, P = 0.006). The main predictor of increases in R5 with LBPP was increases in TFV (r = 0.73, P = 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 cmH2O·l-1·s-1, P = 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.NEW & NOTEWORTHY 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.

Background: We have previously shown that when asthmatics go supine, fluid shifts out of the legs, accumulates in the thorax, and exacerbates lower airway narrowing. In the retrospective analysis of our previous work presented here, we test the hypothesis that the sensitivity of this process relates inversely to baseline caliber of the lower airways. Methods: Eighteen healthy (six women) and sixteen asthmatic subjects (nine women) sat for 30 min, and then lay supine for 30 min. While supine, lower body positive pressure (LBPP, 40 mm Hg) was applied to displace fluid from the legs similar in amount to the overnight fluid shift. Respiratory resistance and reactance at 5 Hz (R5 and X5) and leg and thoracic fluid volumes (LFV and TFV) were measured at the beginning and end of the supine period. Results: With LBPP, healthy, and asthmatic subjects had similar changes in the LFV and TFV (p = 0.3 and 0.1, respectively). Sensitivity to fluid shift, defined by ΔR5/ΔTFV, was larger in the asthmatics than in the healthy subjects (p = 0.0001), and correlated with baseline R5 in the supine position in the asthmatics (p = 0.7, p = 0.003). No such association was observed in the healthy subjects (p = 0.6). In the asthmatics, women showed a greater reduction in X5 than men with LBPP (p = 0.009). Conclusions: Smaller baseline airway caliber, as assessed by larger R5, was associated with increased sensitivity to fluid shift in the supine position. We conclude that asthmatics with narrower small airways such as obese asthma patients, women with asthma and those with severe asthma may be more sensitive to the effects fluid shift while supine as during sleep.

Modelling resistance and reactance with heterogeneous airway narrowing in mild to severe asthma.

Ventilation heterogeneity is an important marker of small airway dysfunction in asthma. The frequency dependence of respiratory system resistance (Rrs) from oscillometry is used as a measure of this heterogeneity. However, this has not been quantitatively assessed or compared with other outcomes from oscillometry, including respiratory system reactance (Xrs) and the associated elastance (Ers). Here, we used a multibranch model of the human lung, including an upper airway shunt, to match previously reported respiratory mechanics in mild to severe asthma. We imposed heterogeneity by narrowing a proportion of the peripheral airways to account for patient Ers at 5 Hz, and then narrowed central airways to account for the remaining Rrs at 18 Hz. The model required >75% of the small airways to be occluded to reproduce severe asthma. While the model produced frequency dependence in Rrs, it was upward-shifted below 5 Hz compared with in-vivo results, indicating that other factors, including more distributed airway narrowing or central airway wall compliance, are required. However, Ers quantitatively reflected the imposed heterogeneity better than the frequency dependence of Rrs, independent of the frequency range for the estimation, and thus was a more robust measure of small-airway function. Thus, Ers appears to have greater potential as a clinical measure of early small-airway disease in asthma.

Oscillatory Mechanics in Asthma: Emphasis on Airway Variability and Heterogeneity.

Spirometry is one of the most widely used tests in the assessment and monitoring of asthma. However, spirometry cannot be performed in very young children and some adult patients, and is poorly sensitive to small airways, which are primarily involved in the pathophysiology of asthma. The forced oscillation technique (FOT) has emerged as a powerful alternative technique that instead characterizes respiratory mechanics during normal breathing with no forced maneuver. In this review we highlight the current state of the art of the FOT and its utility in the assessment of lung function in asthma. First we briefly discuss the clinical features and characteristics of asthma. This is followed by a discussion of the assessment of airway obstruction and airway hyperresponsiveness using spirometry. We then review the basics of FOT and its application in respiratory diseases. FOT data are particularly amenable to modeling as an aide to physiological interpretation, and we review several common approaches. This is followed by an in-depth discussion of the assessment of airway variability and heterogeneity using FOT in asthma. Finally, we speculate on the potential clinical utility of FOT in asthma.

A study of artifacts and their removal during forced oscillation of the respiratory system.

Respiratory impedance measured by the forced oscillation technique (FOT) can be contaminated by artifacts such as coughing, vocalization, swallowing or leaks at the mouthpiece. We present a novel technique to detect these artifacts using multilevel discrete wavelet transforms. FOT was performed with artifacts introduced during separate 60 s recordings at known times in 10 healthy subjects. Brief glottal closures were generated phonetically and confirmed by nasopharyngoscopic imaging of the glottis. Artifacts were detected using Daubechies wavelets by applying a threshold to squared detail coefficients from the wavelet transforms of both pressure and flow signals. Sensitivity and specificity were compared over a range of thresholds for different level squared detail coefficients. Coughs could be identified using 1st level detail (cd1) coefficients of pressure achieving 96% sensitivity and 100% specificity while swallowing could be identified using cd2 thresholds of pressure with 95% sensitivity and 97% specificity. Male vocalizations could be identified using cd1 coefficients with 88% sensitivity and 100% specificity. For leaks at the mouthpiece, cd3 thresholds of flow could identify these events with 98% sensitivity and 99% specificity. Thus, this method provided an accurate, easy, and automated technique for detecting and removing artifacts from measurements of respiratory impedance using FOT.

Modeling stochastic and spatial heterogeneity in a human airway tree to determine variation in respiratory system resistance.

Asthma is a variable disease with changes in symptoms and airway function over many time scales. Airway resistance (Raw) is variable and thought to reflect changes in airway smooth muscle activity, but just how variation throughout the airway tree and the influence of gas distribution abnormalities affect Raw is unclear. We used a multibranch airway lung model to evaluate variation in airway diameter size, the role of coherent regional variation, and the role of gas distribution abnormalities on mean Raw (Raw) and variation in Raw as described by the SD (SDRaw). We modified an anatomically correct airway tree, provided by Merryn Tawhai (The University of Auckland, New Zealand), consisting of nearly 4,000 airways, to produce temporal and spatial heterogeneity. As expected, we found that increasing the diameter variation by twofold, with no change in the mean diameter, increased SDRaw more than fourfold. Perhaps surprisingly, Raw was proportional to SDRaw under several conditions-when either mean diameter was fixed, and its SD varied or when mean diameter varied, and SD was fixed. Increasing the size of a regional absence in gas distribution (ventilation defect) also led to a proportionate increase in both Raw and SDRaw. However, introducing regional dependence of connected airways strongly increased SDRaw by as much as sixfold, with little change in Raw. The model was able to predict previously reported Raw distributions and correlation of SDRaw on Raw in healthy and asthmatic subjects. The ratio of SDRaw to Raw depended most strongly on interairway coherent variation and only had a slight dependence on ventilation defect size. These findings may explain the linear correlation between variation and mean values of Raw but also suggest that regional alterations in gas distribution and local coordination in ventilation amplify any underlying variation in airway diameters throughout the airway tree.