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Background and Objective: The reduction of forced expiratory volume in 1 s (FEV 1 ) in response to methacholine challenge in asthma may reflect two components: airway narrowing, assessed by the change in FEV 1 /forced vital capacity (FVC), and airway closure, assessed by the change in FVC. The purpose of this study was to determine the degree and determinants of airway closure in response to methacholine in a large group of asthmatic patients participating in studies conducted by the American Lung Association-Airways Clinical Research Centers (ALA-ACRC)., Methods: We used the methacholine challenge data from participants in five studies of the ALA-ACRC to determine the closing index, defined as the contribution of airway closure to the decrease in FEV 1 , and calculated as %ΔFVC/%ΔFEV 1 ., Results: There were a total of 936 participants with asthma, among whom the median closing index was 0.67 relative to that of a published healthy population of 0.54. A higher closing index was associated with increased age (10-year increments) (0.04, 95% CI = 0.02, 0.05, P < 0.005) and obesity (0.07, 95% CI = 0.03, 0.10, P < 0.001). There was no association between the closing index and asthma control., Conclusion: Our findings confirm that airway closure in response to methacholine occurs in a large, diverse population of asthmatic participants, and that increased airway closure is associated with older age and obesity. These findings suggest that therapies targeting airway closure may be important in patients with a high closing index., (© 2019 Asian Pacific Society of Respirology.)

Background and Objective: There appears to be two distinct clinical phenotypes of obese patients with asthma-those with early-onset asthma and high serum IgE (TH2-high), and those with late-onset asthma and low serum IgE (TH2-low). The aim of the present study was to determine in the two phenotypes of obese asthma the effect of weight loss on small airway function., Methods: TH2-low (n = 8) and TH2-high (n = 5) obese asthmatics underwent methacholine challenge before and 12 months following bariatric surgery. Dose-response slopes as measures of sensitivity to airway closure and narrowing were measured as maximum % fall forced vital capacity (FVC) and forced expiratory volume in 1 s/FVC, respectively, divided by dose. Resting airway mechanics were measured by forced oscillation technique., Results: Weight loss reduced sensitivity to airway closure in TH 2-low but not TH2-high obese asthmatics (pre-post mean change ± 95% confidence interval: 1.8 ± 0.8 doubling doses vs -0.3 ± 1.7 doubling doses, P = 0.04). However, there was no effect of weight loss on the sensitivity to airway narrowing in either group (P = 0.8, TH2-low: 0.8 ± 1.0 doubling doses, TH2-high: -1.1 ± 2.5 doubling doses). In contrast, respiratory resistance (20 Hz) improved in TH2-high but not in TH2-low obese asthmatics (pre-post change median interquartile range: 1.5 (1.3-2.8) cmH₂O/L/s vs 0.6 (-1.8-0.8) cmH₂O/L/s, P = 0.03)., Conclusions: TH2-low obese asthmatics appear to be characterized by increased small airway responsiveness and abnormalities in resting airway function that may persist following weight loss. However, this was not the case for TH2-high obese asthmatics, highlighting the complex interplay between IgE status and asthma pathophysiology in obesity., (© 2014 Asian Pacific Society of Respirology.)

Rationale: The pathogenesis of asthma in obesity is poorly understood, but may be related to breathing at low lung volumes., Objectives: To determine if lung function in obese patients with asthma and control subjects would respond differently to weight loss., Methods: Lung function was evaluated by conventional clinical tests and by impulse oscillometry in female late-onset, nonallergic patients with asthma and control subjects before, and 12 months after, bariatric surgery., Measurements and Main Results: Patients with asthma (n = 10) had significantly lower FEV1 (79.8 ± 10.6 vs. 95.5 ± 7.0%) and FVC (82.4 ± 13.2 vs. 93.7 ± 8.9%) compared with control subjects (n = 13). There were no significant differences in FRC or TLC at baseline. Twelve months after surgery, control subjects had significant increases in FEV1 (95.5 ± 7.0 to 100.7 ± 5.9), FVC (93.6 ± 8.9 to 98.6 ± 8.3%), FRC (45.4 ± 18.5 to 62.1 ± 15.3%), and TLC (84.8 ± 15.0 to 103.1 ± 15.3%), whereas patients with asthma had improvement only in FEV1 (79.8 ± 10.6 to 87.2 ± 11.5). Control subjects and patients with asthma had a significantly different change in respiratory system resistance with weight loss: control subjects exhibited a uniform decrease in respiratory system resistance at all frequencies, whereas patients with asthma exhibited a decrease in frequency dependence of resistance. Fits of a mathematical model of lung mechanics to these impedance spectra suggest that the lung periphery was more collapsed by obesity in patients with asthma compared with control subjects., Conclusions: Weight loss decompresses the lung in both obese control subjects and patients with asthma, but the more pronounced effects of weight loss on lung elastance suggest that the distal lung is inherently more collapsible in people with asthma.

Background: Asthma in obese subjects is poorly understood, and these patients are often refractory to standard therapy., Objectives: We sought to gain insights into the pathogenesis and treatment of asthma in obese subjects by determining how obesity and bariatric surgery affect asthma control, airway hyperresponsiveness (AHR), and markers of asthmatic inflammation., Methods: We performed a prospective study of (1) asthmatic and nonasthmatic patients undergoing bariatric surgery compared at baseline and (2) asthmatic patients followed for 12 months after bariatric surgery., Results: We studied 23 asthmatic and 21 nonasthmatic patients undergoing bariatric surgery. At baseline, asthmatic patients had lower FEV(1) and forced vital capacity and lower numbers of lymphocytes in bronchoalveolar lavage fluid. After surgery, asthmatic participants experienced significant improvements in asthma control (asthma control score, 1.55 to 0.74; P < .0001) and asthma quality of life (4.87 to 5.87, P < .0001). Airways responsiveness to methacholine improved significantly (methacholine PC(20), 3.9 to 7.28, P = .03). There was a statistically significant interaction between IgE status and change in airways responsiveness (P for interaction = .01). The proportion of lymphocytes in bronchoalveolar lavage fluid and the production of cytokines from activated peripheral blood CD4(+) T cells increased significantly., Conclusions: Bariatric surgery improves AHR in obese asthmatic patients with normal serum IgE levels. Weight loss has dichotomous effects on airway physiology and T-cell function typically involved in the pathogenesis of asthma, suggesting that obesity produces a unique phenotype of asthma that will require a distinct therapeutic approach., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

The increase in asthma associated with the obesity epidemic cannot simply be due to airway hyperresponsiveness from chronic lung compression because chronic lung compression is a feature of obesity in general. We therefore sought to investigate what other factors might be at play in the impaired lung function seen in obese individuals with asthma. We measured respiratory system impedance in four groups—Lean Control, Lean Allergic Asthma, Obese Control, and Obese Allergic Asthma—before and after administration of albuterol. Impedance measurements were fit with an anatomically based computational model of lung mechanics that represents the airway tree as a branching structure with a uniform degree of asymmetry and a fixed radius scaling ratio, γ, between branches of sequential order. The two model parameters that define the airway tree, γ and tracheal radius, varied only modestly between the four study groups, indicating relatively minor differences in airway caliber. In contrast, respiratory system elastance was 57, 34, 143, and 271 cmH2O/L, respectively, for the four groups, suggesting that obesity induced significant lung de-recruitment that was exacerbated by allergic asthma. In addition, when the radii of the individual branches of the airway tree were varied randomly, we found that roughly half the terminal airways had to be closed to have the model fit the data well. We conclude that de-recruitment of small airways is a particular feature of Obese Allergic Asthma, and this can be inferred from respiratory system impedance fit with an anatomically based computational model. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and objective: Obesity produces restrictive effects on lung function. We previously reported that obese patients with asthma exhibit a propensity towards small airway closure during methacholine challenge which improved with weight loss. We hypothesized that increased abdominal adiposity, a key contributor to the restrictive effects of obesity on the lung, mediates this response. This study investigates the effect of body mass index (BMI) versus waist circumference (WC) on spirometric lung function, sensitivity to airway narrowing and closure, and airway closure during bronchoconstriction in patients with asthma. Methods: Participants underwent spirometry and methacholine challenge. Sensitivity to airway closure and narrowing was assessed from the dose–response slopes of the forced vital capacity (FVC) and the ratio of forced expiratory volume in 1 s (FEV1) to FVC, respectively. Airway closure during bronchoconstriction (closing index) was computed as the percent reduction in FVC divided by the percent reduction in FEV1 at maximal bronchoconstriction. Results: A total of 116 asthmatic patients (56 obese) underwent methacholine challenge. Spirometric lung function was inversely related to WC (P < 0.05), rather than BMI. Closing index increased significantly during bronchoconstriction in obese patients and was related to increasing BMI (P = 0.01), but not to WC. Sensitivity to airway closure and narrowing was not associated with BMI or WC. Conclusion: Although WC is associated with restrictive effects on baseline lung function, increased BMI, rather than WC, predisposes to airway closure during bronchoconstriction. These findings suggest that obesity predisposes to airway closure during bronchoconstriction through mechanisms other than simple mass loading. [ABSTRACT FROM AUTHOR]

BACKGROUND: Current American Thoracic Society/European Respiratory Society guidelines recommend that patients hold their breath with minimum effort at total lung capacity during measurement of the single-breath diffusing capacity of the lung for carbon monoxide (DLCO) to avoid excessively positive or negative mouth pressures. We asked to what extent do these pressures range during single-breath DLCO testing and whether mouth pressures are associated with single-breath DLCO. METHODS: We analyzed mouth pressures measured during clinical single-breath DLCO testing in an academic pulmonary function laboratory over a 3-month period. We compared mouth pressures with single-breath DLCO and determined the influence of obesity, restriction, and emphysema on mouth pressures. We used multiple linear regression to evaluate whether mouth pressure was an independent determinant of single-breath DLCO. RESULTS: We analyzed data from 336 subjects who presented with a variety of diseases, the most common of which were unexplained dyspnea, interstitial lung disease, sarcoidosis, and emphysema. The median mouth pressure was 4.5 cm H2O, with a range of -13 to 31 cm H2O. The single-breath DLCO did not correlate with mouth pressure (P = .08). There was no difference in mouth pressures between individuals with and without obesity, with and without restriction, and with and without interstitial lung disease. Mouth pressure was lower among the subjects with emphysema. There was no difference in single-breath DLCO % predicted between individuals who were obese and individuals who were not obese. Multiple linear regression demonstrated that only age and FEV1, but not mouth pressure, were independently associated with single-breath DLCO % predicted (β-coefficient: age, -0.35 [P = .003]; FEV1%, 0.26 [P = .004]; adjusted R², 0.16). CONCLUSIONS: Mouth pressures varied widely during single-breath DLCO measurement but were not associated with the measurement of single-breath DLCO in the clinical setting of pulmonary function testing. Overall, these findings indicate that pulmonary function technologists need not discard efforts made during measurement of single-breath DLCO if only mild changes in mouth pressure occur. [ABSTRACT FROM AUTHOR]

The article discusses a research study conducted to assess the prevalence of airflow limitation in patients with emphysema on computerized tomography (CT) scan based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) and lower limit of normal (LLN) criteria. Topics covered include the revised GOLD classification for chronic obstructive pulmonary disease (COPD), the effects of obesity on spirometry, and radiologic criteria specific to patients with radiographic emphysema and COPD.