Reference Equations for Within-Breath Respiratory Oscillometry in White Adults.

BACKGROUND: Within-breath analysis of oscillometry parameters is a growing research area since it increases sensitivity and specificity to respiratory pathologies and conditions. However, reference equations for these parameters in White adults are lacking and devices using multiple sinusoids or pseudorandom forcing stimuli have been underrepresented in previous studies deriving reference equations. The current study aimed to establish reference ranges for oscillometry parameters, including also the within-breath ones in White adults using multi-sinusoidal oscillations. METHODS: White adults with normal spirometry, BMI ≤30 kg/m2, without a smoking history, respiratory symptoms, pulmonary or cardiac disease, neurological or neuromuscular disorders, and respiratory tract infections in the previous 4 weeks were eligible for the study. Study subjects underwent oscillometry (multifrequency waveform at 5-11-19 Hz, Resmon PRO FULL, RESTECH Srl, Italy) in 5 centers in Europe and the USA according to international standards. The within-breath and total resistance (R) and reactance (X), the resonance frequency, the area under the X curve, the frequency dependence of R (R5-19), and within-breath changes of X (ΔX) were submitted to lambda-mu-sigma models for deriving reference equations. For each output parameter, an AIC-based stepwise input variable selection procedure was applied. RESULTS: A total of 144 subjects (age 20.8-86.3 years; height 146-193 cm; BMI 17.42-29.98 kg/m2; 56% females) were included. We derived reference equations for 29 oscillatory parameters. Predicted values for inspiratory and expiratory parameters were similar, while differences were observed for their limits of normality. CONCLUSIONS: We derived reference equations with narrow confidence intervals for within-breath and whole-breath oscillatory parameters for White adults.

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.

Altered airway mechanics in the context of obesity and asthma.

The obesity epidemic is causing a rise in asthma incidence due to the appearance of an obesity-specific late-onset nonallergic (LONA) phenotype. We investigated why only a subset of obese participants develop LONA asthma by determining how obesity, both alone and in combination with LONA asthma, affects the volume dependence of respiratory system impedance. We also determined how obesity and asthma affect impedance during and following challenge with the PC20 dose of methacholine. We found during passive exhalation that all obese participants, in contrast to lean controls and lean asthmatics, experienced similarly profound elevations in lung elastance as they approached functional residual capacity. We also found, however, that the LONA asthmatics had a greater negative dependence of airway resistance on lung volume over the middle of the volume range compared with the other groups. Methacholine challenge with the PC20 dose led to comparable changes in respiratory system impedance in the four study groups, but the doses themselves were substantially lower in both obese and lean asthmatic participants compared with obese and lean controls. Also, the obese LONA asthmatics had higher breathing frequencies and lower tidal volumes postchallenge compared with the other participants. Taken together, these results suggest that all obese individuals experience substantial lung collapse as they approach functional residual capacity, presumably due to the weight of the chest wall. It remains unclear why obese LONA asthmatics are hyperresponsive to methacholine while obese nonasthmatic individuals are not.NEW & NOTEWORTHY Why only a subset of severely obese subjects develop late-onset nonallergic (LONA) asthma remains unknown, although it is widely assumed that compression of the lungs by the chest wall is somehow involved. We show that lung compression is common to obese individuals both without asthma and with LONA asthma but that those with LONA asthma may have increased airway wall compliance and possibly also a reduced ability to recruit collapsed lung.

Physiological signature of late-onset nonallergic asthma of obesity.

INTRODUCTION: Obesity can lead to a late-onset nonallergic (LONA) form of asthma for reasons that are not understood. We sought to determine whether this form of asthma is characterised by any unique physiological features. METHODS: Spirometry, body plethysmography, multiple breath nitrogen washout (MBNW) and methacholine challenge were performed in four subject groups: Lean Control (n=11), Lean Asthma (n=11), Obese Control (n=11) and LONA Obese Asthma (n=10). The MBNW data were fitted with a novel computational model that estimates functional residual capacity (FRC), dead space volume (VD), the coefficient of variation of regional specific ventilation (CV,V'E) and a measure of structural asymmetry at the level of the acinus (sacin). RESULTS: Body mass index and waist circumference values were similar in both obese groups, and significantly greater than in lean asthmatic individuals and controls. Forced vital capacity was significantly lower in the LONA Asthma group compared with the other groups (p<0.001). Both asthma groups exhibited similar hyperresponsiveness to methacholine. FRC was reduced in the Obese LONA Asthma group as measured by MBNW, but not in obese controls, whereas FRC was reduced in both obese groups as measured by plethysmography. VD, CV,V'E and sacin were not different between groups. CONCLUSIONS: Chronic lung compression characterises all obese subjects, as reflected by reduced plethysmographic FRC. Obese LONA asthma is characterised by a reduced ability to recruit closed lung units, as seen by reduced MBNW FRC, and an increased tendency for airway closure as seen by a reduced forced vital capacity.

Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children.

BACKGROUND: Exhaled nitric oxide (eNO) is a noninvasive test that measures airway inflammation. Insufficient information is available concerning correlations between eNO and biologic, physiologic, and clinical characteristics of asthma in children currently not taking controller medications. OBJECTIVE: The aim of this study was to find correlations between eNO and other characteristics of children with mild to moderate asthma currently not taking medications. METHODS: Children aged 6 to 17 years with mild to moderate persistent asthma, taking only albuterol as needed, were characterized during 2 visits 1 week apart before being randomly assigned into a clinical trial. At the screening visit, online measurements of eNO, spirometry before and after bronchodilator, and biomarkers of peripheral blood eosinophils, serum eosinophil cationic protein, total serum IgE, and urinary leukotriene E4 were obtained. During a week characterization period before randomization, symptoms were recorded on a diary and peak expiratory flows were measured twice daily using an electronic device. At the randomization visit, eNO was repeated followed by a methacholine challenge and aeroallergen skin testing. Correlations and rank regression analyses between eNO and clinical characteristics, pulmonary function, and biomarkers were evaluated. RESULTS: eNO was significantly correlated with peripheral blood eosinophils (r =.51, P <.0001), IgE (r =.48, P <.0001), and serum eosinophil cationic protein (r =.31, P =.0003) but not with urinary leukotriene E4 (r =.16, P =.08). A moderate correlation was found between eNO and the number of positive aeroallergen skin tests (r =.45, P <.0001). eNO did not correlate with FEV1% predicted but was weakly correlated with FEV1/forced vital capacity (r = -.19, P =.032), bronchodilator response (r =.20, P =.023), and FEV1 PC20 methacholine (r = -.31, P =.0005). No significant correlations were found between eNO and clinical characteristics or morning or evening peak expiratory flow measurements. The rank regression analysis demonstrated that 5 variables accounted for an R square of.52 (eosinophils [P <.0001], IgE [P =.0023], age [P <.0001], months of inhaled corticosteroid use in the year before study entry [P =.01], and FEV1 PC20 [P =.0061]). CONCLUSIONS: These findings suggest that eNO provides information about the asthmatic state consistent with information from other markers of inflammation. It is a noninvasive technique that could be used in decisional management of children with asthma.