Peripheral Airway Dysfunction in Obesity and Obese Asthma
2023; Elsevier BV; Volume: 163; Issue: 4 Linguagem: Inglês
10.1016/j.chest.2022.12.030
ISSN1931-3543
AutoresAnne E. Dixon, Matthew E. Poynter, Olivia Johnson Garrow, David A. Kaminsky, William G. Tharp, Jason H. T. Bates,
Tópico(s)Chronic Obstructive Pulmonary Disease (COPD) Research
ResumoBackgroundThe purpose of this study was to investigate physiological phenotypes of asthma in obesity.Research QuestionDo physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity?Study Design and MethodsCross-sectional study of people with obesity (31 with asthma and 22 without lung disease). Participants underwent methacholine challenge testing with measurement of spirometry and respiratory system impedance by oscillometry.ResultsParticipants had class III obesity (BMI, 46.7 ± 6.6 kg/m2 in control subjects and 47.2 ± 8.2 kg/m2 in people with asthma). Most participants had significant changes in peripheral airway impedance in response to methacholine: in control subjects, resistance at 5 Hz measured by oscillometry increased by 45% ± 27% and area under the reactance curve (AX) by 268% ± 236% in response to 16 mg/mL methacholine; in people with asthma, resistance at 5 Hz measured by oscillometry increased by 52% ± 38% and AX by 361% ± 295% in response to provocation concentration producing a 20% fall in FEV1 dose of methacholine. These responses suggest that obesity predisposes to peripheral airway reactivity. Two distinct groups of asthma emerged based on respiratory system impedance: one with lower reactance (baseline AX, 11.8; interquartile range, 9.9-23.4 cm H2O/L) and more concordant bronchoconstriction in central and peripheral airways; the other with high reactance (baseline AX, 46.7; interquartile range, 23.2-53.7 cm H2O/L) and discordant bronchoconstriction responses in central and peripheral airways. The high reactance asthma group included only women, and reported significantly more gastroesophageal reflux disease, worse chest tightness, more wheeze, and more asthma exacerbations than the low reactance group.InterpretationPeripheral airway reactivity detected by oscillometry is common in obese control subjects and obese people with asthma. There is a subgroup of obese asthma characterized by significant peripheral airway dysfunction by oscillometry out of proportion to spirometric airway dysfunction. This peripheral dysfunction represents clinically significant respiratory disease not readily assessed by spirometry. The purpose of this study was to investigate physiological phenotypes of asthma in obesity. Do physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity? Cross-sectional study of people with obesity (31 with asthma and 22 without lung disease). Participants underwent methacholine challenge testing with measurement of spirometry and respiratory system impedance by oscillometry. Participants had class III obesity (BMI, 46.7 ± 6.6 kg/m2 in control subjects and 47.2 ± 8.2 kg/m2 in people with asthma). Most participants had significant changes in peripheral airway impedance in response to methacholine: in control subjects, resistance at 5 Hz measured by oscillometry increased by 45% ± 27% and area under the reactance curve (AX) by 268% ± 236% in response to 16 mg/mL methacholine; in people with asthma, resistance at 5 Hz measured by oscillometry increased by 52% ± 38% and AX by 361% ± 295% in response to provocation concentration producing a 20% fall in FEV1 dose of methacholine. These responses suggest that obesity predisposes to peripheral airway reactivity. Two distinct groups of asthma emerged based on respiratory system impedance: one with lower reactance (baseline AX, 11.8; interquartile range, 9.9-23.4 cm H2O/L) and more concordant bronchoconstriction in central and peripheral airways; the other with high reactance (baseline AX, 46.7; interquartile range, 23.2-53.7 cm H2O/L) and discordant bronchoconstriction responses in central and peripheral airways. The high reactance asthma group included only women, and reported significantly more gastroesophageal reflux disease, worse chest tightness, more wheeze, and more asthma exacerbations than the low reactance group. Peripheral airway reactivity detected by oscillometry is common in obese control subjects and obese people with asthma. There is a subgroup of obese asthma characterized by significant peripheral airway dysfunction by oscillometry out of proportion to spirometric airway dysfunction. This peripheral dysfunction represents clinically significant respiratory disease not readily assessed by spirometry. Take-home PointsStudy Question: Do physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity?Results: A subgroup of people with obesity and asthma have significant dysfunction in the distal airways at baseline that worsens with methacholine. This subgroup report increased symptoms and increased asthma exacerbations, suggesting this distal airway dysfunction is clinically significant. Many obese people without asthma also develop distal airway dysfunction in response to moderate doses of methacholine.Interpretation: Oscillometry testing can reveal a physiological phenotype of asthma in obesity that may be related to worse symptoms and more severe disease, and also reveal subclinical abnormalities in people with obesity, but without clinically diagnosed lung disease. Study Question: Do physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity? Results: A subgroup of people with obesity and asthma have significant dysfunction in the distal airways at baseline that worsens with methacholine. This subgroup report increased symptoms and increased asthma exacerbations, suggesting this distal airway dysfunction is clinically significant. Many obese people without asthma also develop distal airway dysfunction in response to moderate doses of methacholine. Interpretation: Oscillometry testing can reveal a physiological phenotype of asthma in obesity that may be related to worse symptoms and more severe disease, and also reveal subclinical abnormalities in people with obesity, but without clinically diagnosed lung disease. Obesity is associated with an increased risk of asthma. People with obesity also tend to have worse asthma control and more severe disease than lean people with asthma,1Peters U. Dixon A.E. Forno E. Obesity and asthma.J Allergy Clin Immunol. 2018; 141: 1169-1179Google Scholar and approximately 60% of adults with severe asthma in the United States are obese.2Teague W.G. Phillips B.R. Fahy J.V. et al.Baseline Features of the Severe Asthma Research Program (SARP III) cohort: differences with age.J Allergy Clin Immunol Pract. 2018; 6: 545-554.e544Google Scholar Obesity can cause respiratory symptoms that overlap with those of asthma (eg, dyspnea, exercise intolerance), complicating our understanding of asthma in obesity. There is a pressing need to understand the pathophysiology of obese asthma to design better treatments. We previously identified a group of individuals with obesity and late-onset nonallergic (LONA) asthma characterized by minimal airway inflammation but with airway reactivity and symptoms that improve with weight loss, which appears distinct from early-onset allergic asthma in people with obesity.3Dixon A.E. Pratley R.E. Forgione P.M. et al.Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation.J Allergy Clin Immunol. 2011; 128 (e501-502): 508-515Google Scholar,4Al-Alwan A. Bates J.H. Chapman D.G. et al.The nonallergic asthma of obesity. A matter of distal lung compliance.Am J Respir Crit Care Med. 2014; 189: 1494-1502Google Scholar However, asthma is a complex syndrome defined by a constellation of features; therefore, there are likely multiple ways in which obese asthma can be partitioned into different phenotypes. Given our data in humans5Sideleva O. Suratt B.T. Black K.E. et al.Obesity and asthma: an inflammatory disease of adipose tissue not the airway.Am J Respir Crit Care Med. 2012; 186: 598-605Google Scholar and animal models of obesity6Ather J.L. Chung M. Hoyt L.R. et al.Weight loss decreases inherent and allergic methacholine hyperresponsiveness in mouse models of diet-induced obese asthma.Am J Respir Cell Mol Biol. 2016; 55: 176-187Google Scholar suggesting airway reactivity in obesity can occur without airway inflammation, we wondered if phenotyping obese asthma according to lung function characteristics might provide insight into the nature of the disease. Distinct aspects of lung function may be affected in airway disease. Asthma is conventionally characterized by the spirometric parameters FEV1, FVC, and FEV1/FVC ratio.7Crapo R.O. Casaburi R. Coates A.L. et al.Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999.Am J Respir Crit Care Med. 2000; 161: 309-329Google Scholar These quantities can be complemented by parameters derived from oscillometry, a technique in which an oscillating signal is administered to the respiratory system at different frequencies and the fluctuations in pressure and flow measured at the mouth are used to calculate respiratory system impedance.8King G.G. Bates J. Berger K.I. et al.Technical standards for respiratory oscillometry.Eur Respir J. 2020; 55: 1900753Google Scholar,9Bhatawadekar S.A. Leary D. de Lange V. et al.Reactance and elastance as measures of small airways response to bronchodilator in asthma.J Appl Physiol. 2019; 127: 1772-1781Google Scholar Impedance can be subdivided into (1) respiratory system resistance (resistance to airflow that is largely reflective of airway caliber) and (2) respiratory system reactance (elastic properties of the respiratory system tissues). Impedance at high frequencies tends to reflect the properties of proximal airways, whereas impedance at low frequencies reflects more distal airways. The difference between resistance at 5 and 19 Hz (R5-19), termed frequency dependence of resistance, is frequently used as a measure of airway heterogeneity and increased resistance in the peripheral airways. The area under the reactance curve (AX) between 5 Hz and the resonant frequency is an integrated measure reflecting stiffness of the respiratory system.8King G.G. Bates J. Berger K.I. et al.Technical standards for respiratory oscillometry.Eur Respir J. 2020; 55: 1900753Google Scholar Interestingly, Oppenheimer et al10Oppenheimer B.W. Goldring R.M. Soghier I. Smith D. Parikh M. Berger K.I. Small airway function in obese individuals with self-reported asthma.ERJ Open Res. 2020; 6: 00371-2019Google Scholar reported that some people with obesity and asthma may have normal spirometry but exhibit small airways dysfunction as measured by oscillometry. It therefore appears that combining spirometry and oscillometry might reveal abnormalities in lung mechanics particularly pertinent to people with obesity and asthma. The goal of this study was to use spirometry and oscillometry during methacholine-induced bronchoconstriction to identify physiological phenotypes of obese asthma, to determine how these characteristics differ from lung function abnormalities in people with obesity but without asthma, and to understand what this implies for our understanding of obese asthma pathophysiology. Understanding differences in lung function abnormalities between obese people with and without asthma, and among asthmatic phenotypes, will help improve diagnosis and treatment of asthma in people with obesity. We recruited participants being evaluated for bariatric surgery at the University of Vermont Medical Center. The University of Vermont institutional review board approved the protocol (No. 16-541), and all participants signed informed consent. Eligibility criteria included ≥ 18 years of age and FEV1 of at least 60% predicted. Participants were excluded if they had a chronic lung disease other than asthma, ≥ 20 pack-years of smoking history, had smoked within the last 6 months, or were pregnant. Participants with asthma had to have been previously diagnosed with asthma by a physician and to have physiological evidence of asthma with airway reactivity to methacholine by either spirometry or oscillometry (as we have previously noticed that many obese people with asthma respond significantly by oscillometry); we defined airway reactivity as either a 20% fall in FEV1 and/or a 50% change in resistance or reactance at 5 Hz (resistance at 5 Hz measured by oscillometry [R5] and reactance at 5 Hz measured by oscillometry [X5]), at a concentration of ≤ 16 mg/mL of methacholine.7Crapo R.O. Casaburi R. Coates A.L. et al.Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999.Am J Respir Crit Care Med. 2000; 161: 309-329Google Scholar,8King G.G. Bates J. Berger K.I. et al.Technical standards for respiratory oscillometry.Eur Respir J. 2020; 55: 1900753Google Scholar Control subjects were identified as people without a physician diagnosis of asthma (or other lung disease) who experienced < 20% fall in FEV1, regardless of oscillometry response, at a concentration of 16 mg/mL methacholine. Testing was completed at a single visit. Participants with asthma completed an asthma control questionnaire.11Juniper E.F. O'Byrne P.M. Guyatt G.H. Ferrie P.J. King D.R. Development and validation of a questionnaire to measure asthma control.Eur Respir J. 1999; 14: 902-907Google Scholar Conventional lung function was assessed using a pneumotachograph spirometer and body plethysmograph (Medgraphics Platinum Elite) as per American Thoracic Society/European Respiratory Society guidelines.12Miller M.R. Hankinson J. Brusasco V. et al.Standardisation of spirometry.Eur Respir J. 2005; 26: 319-338Google Scholar,13Wanger J. Clausen J.L. Coates A. et al.Standardisation of the measurement of lung volumes.Eur Respir J. 2005; 26: 511-522Google Scholar Results were presented using the National Health and Nutrition Examination Survey III for spirometry14Hankinson J.L. Odencrantz J.R. Fedan K.B. Spirometric reference values from a sample of the general U.S. population.Am J Respir Crit Care Med. 1999; 159: 179-187Google Scholar and Goldman and Becklake15Goldman H.I. Becklake M.R. Respiratory function tests; normal values at median altitudes and the prediction of normal results.Am Rev Tuberc. 1959; 79: 457-467Google Scholar for lung volumes. Subjects underwent methacholine aerosol challenge according to the 1999 American Thoracic Society7Crapo R.O. Casaburi R. Coates A.L. et al.Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999.Am J Respir Crit Care Med. 2000; 161: 309-329Google Scholar guidelines using the 2-min tidal breathing protocol administering doubling concentrations of methacholine through a DeVilbiss PulmoAide nebulizer up to a maximum concentration of 16 mg/mL. Testing ended when either the FEV1 dropped by 20% from baseline or 16 mg/mL methacholine had been administered. Oscillometry (Tremoflo; Thorasys) was used to measure impedance between 5 and 19 Hz during quiet tidal breathing for 30 s at baseline, and after the highest dose of methacholine. Oscillometry was performed immediately after spirometry. Participants completed at least two reproducible measurements of impedance, determined by inspection of waveform and coefficient of variation between testing < 15%. We compared continuous variables by t test or Wilcoxon rank sum test (for data that were not normally distributed). Categorical values were compared by χ2 analysis. The relationship between changes in spirometry and respiratory system impedance parameters at the maximal dose of methacholine was assessed using Spearman correlation. All analyses were performed using STATA 16.0 (StataCorp). Demographic characteristics of the 53 participants (31 people with asthma and 22 without asthma) are shown in Table 1. The groups were well matched in terms of most characteristics; however, participants with asthma had a slightly higher serum IgE, and had more often smoked.Table 1Baseline Demographics of ParticipantsDemographicControl Subjects (n = 22)People With Asthma (n = 31)P ValueFemale18 (82)23 (74).51Age, y39.9 ± 11.143.9 ± 11.8.22BMI, kg/m246.7 ± 6.647.5 ± 81.72Waist circumference, cm128 ± 11133 ± 16.23Gastroesophageal reflux10 (45)18 (58).30Diabetes mellitus2 (9)3 (10).91Age of asthma onset, y…21 ± 10…IgE, International Units/mL12 (3-23)31 (7-102).06Absolute eosinophil, cells/μL180 ± 115196 ± 113.62Inhaled corticosteroid…10 (32)…Long-acting beta-agonist…8 (26)…Long-acting muscarinic antagonist…2 (6)…Leukotriene receptor antagonist…4(13)…Systemic corticosteroidsaReported course of systemic corticosteroids in prior year for an asthma exacerbation.…7 (22)…Ever smoked3 (14)10 (32).05Pack-year (if ever smoked)7.3 ± 6.810.3 ± 4.5.39Asthma Control Score…0.97 ± 1.07…Values are mean ± SD with P values shown for t test for normally distributed data, median (interquartile range) with P value for Wilcoxon rank sum test for nonparametric data, or No. (%) with χ2 test for proportions.a Reported course of systemic corticosteroids in prior year for an asthma exacerbation. Open table in a new tab Values are mean ± SD with P values shown for t test for normally distributed data, median (interquartile range) with P value for Wilcoxon rank sum test for nonparametric data, or No. (%) with χ2 test for proportions. Baseline lung function and respiratory system impedance parameters are shown in Table 2. As expected, those with asthma had lower FEV1, lower FVC, lower FEV1/FVC, higher residual volume, and lower expiratory reserve volume than control subjects. Participants with asthma had higher R5-19, higher AX, and lower X5 than control subjects, suggesting heterogeneity of ventilation and peripheral airway abnormalities at baseline.Table 2Baseline Lung Function of Control Subjects and People With AsthmaLung Function ParameterControl SubjectsPeople With AsthmaP ValueLung function FEV1, L3.63 ± 0.692.72 ± 0.62< .001 FEV1, %101.9 ± 13.488.5 ± 12.7< .001 FVC, L3.97 ± 0.853.44 ± 0.79.02 FVC, %97.8 ± 11.389.8 ± 10.0< .01 FEV1/FVC85 (82 to 88)80 (75 to 87).02 TLC, L5.36 ± 0.945.10 ± 0.87.31 TLC, %96.9 ± 11.496.1± 14.7.85 RV, L1.47 ± 0.451.85 ± 0.51< .01 RV, %84.6 ± 28.0109.6 ± 30.4< .01 IC, L3.27 ± 0.672.89 ± 0.67.04 IC, %123.8 ± 27.5113.0 ± 25.3.14 ERV, L0.69 ± 0.430.37 ± 0.36< .01 ERV, %50.3 ± 25.230.9 ± 27.4.01 FRC, L2.17 ± 0.472.22 ± 0.38.69 FRC, %aFRC percent predicted calculated per Goldman and Becklake,15 using actual height and body surface area for men, and actual height and weight for women.105.3 ± 30.494.5 ± 34.6.25Oscillometry R5, H2O.s.L−15.14 ± 1.456.09 ± 1.87.05 R19, H2O.s.L−14.31 ± 1.064.60 ± 1.14.36 R5-19, H2O.s.L−10.73 (0.28 to 1.28)1.35 (0.69 to 2.10).01 X5, H2O.s.L−1−1.86 (−2.30 to −1.00)−2.45 (−4.23 to −1.97).001 AX, cm H2O/L9.80 (6.49 to 15.68)23.23 (10.67 to 48.22)< .001Values are mean ± SD with P values shown for t test for normally distributed data, or median (interquartile range) with P value for Wilcoxon rank sum test for nonnormally distributed data. Numbers in boldface indicate variables that are significantly different between control and asthma groups. AX = area under the reactance curve; ERV = expiratory reserve volume; FRC = functional residual capacity; IC = inspiratory capacity; R5 = resistance at 5 Hz measured by oscillometry; R5-19 = difference between resistance at 5 and 19 Hz; R19 = resistance at 19 Hz measured by oscillometry; RV = residual volume; TLC = total lung capacity; X5 = reactance at 5 Hz measured by oscillometry.a FRC percent predicted calculated per Goldman and Becklake,15Goldman H.I. Becklake M.R. Respiratory function tests; normal values at median altitudes and the prediction of normal results.Am Rev Tuberc. 1959; 79: 457-467Google Scholar using actual height and body surface area for men, and actual height and weight for women. Open table in a new tab Values are mean ± SD with P values shown for t test for normally distributed data, or median (interquartile range) with P value for Wilcoxon rank sum test for nonnormally distributed data. Numbers in boldface indicate variables that are significantly different between control and asthma groups. AX = area under the reactance curve; ERV = expiratory reserve volume; FRC = functional residual capacity; IC = inspiratory capacity; R5 = resistance at 5 Hz measured by oscillometry; R5-19 = difference between resistance at 5 and 19 Hz; R19 = resistance at 19 Hz measured by oscillometry; RV = residual volume; TLC = total lung capacity; X5 = reactance at 5 Hz measured by oscillometry. Responses to methacholine are shown in Table 3. As anticipated, people with asthma had greater decrements in FEV1 and FVC compared with control subjects, and responded at lower doses. The absolute magnitudes of R5, R5-19, X5, and AX were all greater at peak methacholine in people with asthma (and the peak dose of methacholine was lower); however, only the percent change in X5 was greater in those with asthma compared with control subjects. Indeed, 14 of 22 control subjects had ΔR5 > 50%, and/or ΔX5 > 50% at 16 mg/mL methacholine (e-Table 1). We compared clinical (e-Table 1) and baseline lung function characteristics (e-Table 2) of control subjects with a response in oscillometry parameters at 16 mg/mL of methacholine to control subjects without this response to methacholine. We found no differences in baseline characteristics (although those with an oscillometry response also had a numerically higher BMI and waist circumference). Spirometry response was also greater in this group (e-Table 3). These data suggest a high proportion of people with class III obesity have distal lung dysfunction in response to moderate doses of methacholine, which may represent subclinical airway reactivity.Table 3Response to Peak MethacholineLung Function ParameterControl SubjectsPeople With AsthmaP ValuePeak methacholine, mg/mL16 (16)3.1 (1.0 to 9.5).0001FEV1 % change−7.9 (−14.4 to −2.4)−23.2 (−25.5 to −20.7)< .0001FVC % change−3.9 (−10.6 to −1.6)−17.2 (−22.4 to −13.8)< .0001R5, H2O.s.L−17.31 ± 1.948.94 ± 2.56.02R5 % change44.5 ± 27.251.8 ± 37.5.44R19, H2O.s.L−14.84 ± 1.125.20 ± 1.40.31R19 % change13.5 ± 15.514.1 ± 18.3.91R5-192.47 ± 1.313.74 ± 1.43< .01R5-19 % change309 (111 to 385)123 (84 to 370).24X5, H2O.s.L−1−3.61 (−5.31 to −1.74)−7.94 (−11.9 to −5.32).0001X5 % change109 ± 109189 ± 97< .01AX, cm H2O/L39.4 (15.9 to 53.6)85.7 (57.7 to 125.6).0001AX % change268 ± 236361 ± 295.23Values are mean ± SD with P values shown for t test for normally distributed data, or median (interquartile range) with P value for Kruskal-Wallis test for nonnormally distributed data. Numbers in boldface indicate variables that are significantly different between control and asthma groups. AX = area under the reactance curve; R5 = resistance at 5 Hz measured by oscillometry; R5-19 = difference between resistance at 5 and 19 Hz; R19 = resistance at 19 Hz measured by oscillometry; X5 = reactance at 5 Hz measured by oscillometry. Open table in a new tab Values are mean ± SD with P values shown for t test for normally distributed data, or median (interquartile range) with P value for Kruskal-Wallis test for nonnormally distributed data. Numbers in boldface indicate variables that are significantly different between control and asthma groups. AX = area under the reactance curve; R5 = resistance at 5 Hz measured by oscillometry; R5-19 = difference between resistance at 5 and 19 Hz; R19 = resistance at 19 Hz measured by oscillometry; X5 = reactance at 5 Hz measured by oscillometry. There was a strong correlation between %ΔFEV1 and %ΔFVC in both those with asthma and control participants (Table 4). There was a good correlation of %ΔFEV1 with both %ΔAX and %ΔX5 in control subjects but not participants with asthma (Table 4).Table 4Correlation of Change in FEV1, With Changes in FVC and Impedance Parameters in Response to Methacholine in Control Subjects and People With AsthmaVariableControl SubjectsPeople With AsthmaρP ValueρP ValueChange in FVC0.89< .000.86< .00Change in AX−0.46.03−0.24.19Change in X5−0.59< .01−0.11.54Change in R5−0.35.11−0.21.24Change in R5-19−0.31.17−0.32.08Numbers in boldface indicate variables that are significantly different between control and asthma groups. AX = area under the reactance curve; R5 = resistance at 5 Hz measured by oscillometry; R5-19 = difference between resistance at 5 and 19 Hz; X5 = reactance at 5 Hz measured by oscillometry. Open table in a new tab Numbers in boldface indicate variables that are significantly different between control and asthma groups. AX = area under the reactance curve; R5 = resistance at 5 Hz measured by oscillometry; R5-19 = difference between resistance at 5 and 19 Hz; X5 = reactance at 5 Hz measured by oscillometry. No control subjects had an AX > 94.1 cm H2O/L in response to methacholine. We therefore chose a threshold of AX ≥ 100 cm H2O/L to exclude responses of obese control subjects, and then divided the participants with asthma into two clusters: (1) a low peak bronchoconstriction reactance (AX < 100 cm H2O/L) group and (2) a high peak bronchoconstriction reactance (AX ≥ 100 cm H2O/L) group. Conventional lung function parameters at baseline were similar, but impedance parameters at baseline were significantly more abnormal in the high reactance group (Fig 1, Table 5). In response to methacholine, we found similar percentage changes in most oscillometry parameters with the exception of %ΔX5, which was greater in the high reactance group. The absolute magnitudes of R5, R5-19, and X5 at peak methacholine were greater in the high reactance group, and tidal volume was lower (Table 6). There was a stronger and more significant correlation between changes in impedance parameters and %ΔFEV1 in the low reactance group, particularly R5-19, suggesting greater concordance between central and peripheral airway behavior during bronchoconstriction (Table 7). There were no differences in oscillometry responses or airway reactivity level when comparing those using vs not using inhaled corticosteroids in the high reactance group (median provocation concentration producing a 20% fall in FEV1, 3.8; interquartile range, 2.1-16 vs median, 2.9; interquartile range, 0.8-3.7). The discordance between the changes in impedance parameters and ΔFEV1 in the high reactance group may be caused by greater peripheral than central airway dysfunction. This possibility is supported by similar changes in resistance at 19 Hz measured by oscillometry but greater changes in R5 and X5. This peripheral dysfunction also exists at baseline in the high reactance group (Fig 1, Table 5).Table 5Lung Function Characteristics of High and Low Reactance GroupCharacteristicLow ReactanceHigh ReactanceP ValueLung function FEV1, L3.15 (2.38 to 3.49)2.48 (2.21 to 2.75).05 FEV1, %89 (85 to 97)90 (85 to 93).85 FVC, L3.73 ± 0.853.09 ± 0.56.02 FVC %89.1 ± 11.990.6 ± 7.4.69 FEV1/FVC79.9 ± 10.179.0 ± 6.6.77 TLC, L5.22 ± 0.784.96 ± 0.96.41 TLC, %91.7 ± 13.3101.5 ± 14.9.06 RV, L1.80 ± 0.531.91 ± 0.50.53 RV, %106 ± 36114 ± 23.48 IC, L2.96 ± 0.692.79 ± 0.66.49 IC, %109 ± 21118 ± 30.37 ERV, L0.40 (0.18 to 0.53)0.19 (0.11 to 0.37).18 ERV, %31 (11 to 64)17 (10 to 32).24 FRC, L2.34 (2.08 to 2.49)2.22 (1.81 to 2.44).35 FRC, %77 (71 to 95)98 (80 to 133).07Oscillometry R5, H2O.s.L-14.94 (4.44 to 5.62)7.19 (6.57 to 8.78)< .001 R19, H2O.s.L-13.93 (3.60 to 4.17)5.14 (4.85 to 6.69)< .001 R5-19, H2O.s.L-11.09 (0.57 to 1.35)2.05 (1.49 to 3.11).02 X5, H2O.s.L-1−2.20 (−2.65 to −1.77)−3.70 (−4.59 to −2.39)< .01 AX, cm H2O/L11.8 (9.9 to 23.4)46.7 (23.2 to 53.7).001 Tidal volume, L0.96 (0.82 to 1.47)0.73 (0.68 to 0.83).07Values are mean ± SD with P values shown for t test for normally distributed data, or median (interquartile range) with P value for Kruskal-Wallis test for nonnormally distributed data. Numbers in boldface indicate variables that are significantly different between control and asthma groups. AX = area under the reactance curve; ERV = expiratory reserve volume; FRC = functional residual capacity; IC = inspiratory capacity; R5 = resistance at 5 Hz measured by oscillometry; R5-19 = difference between resistance at 5 and 19 Hz; R19 = resistance at 19 Hz measured by oscillometry; RV = residual volume; TLC = total lung capacity; X5 = reactance at 5 Hz measured by oscillometry. Open table in a new tab Table 6Lung Function Characteristics of Response to Peak Methacholine DoseCharacteristicLow ReactanceHigh ReactanceP ValueMethacholine, mg/mL2.5 (0.6 to 4.6)3.7 (2.1 to 9.5).21FEV1 % change−25.2 (−28.0 to −21.0)−22.1 (−24.4 to −20.7).21FVC % change−18.9 (−22.4 to −16.0)−15.5 (−22.1 to −11.3).54R5, H2O.s.L−17.12 (6.73 to 8.26)10.46 (9.25 to 13.10)< .0001R5 % change42.2 (28.3 to 67.7)52.8 (28.2 to 75.1).67R19, H2O.s.L−14.26 (4.04 to 5.17)5.90 (4.98 to 6.92)< .01R19 % change15.8 (4.1 to 31.2)14.4 (3.0 to 30.1).85R5-192.68 (2.44 to 3.20)4.85 (4.13 to 5.90)< .0001R5-19 % change113 (95 to 399)182 (165 to 320).79X5, H2O.s.L−1−5.96 (−7.40 to −3.84)−13.97 (−13.97 to −9.34)< .0001X5 % change162 (85 to 219)183 (164 to 321).05AX, cm H2O/L64.3 (49.7 to 73.3)126.4 (119.1 to 156.3)aNot compared statistically, as groups defined according to AX.AX % change247 (159 to 531)236 (177 to 423).67Tidal volume, L0.98 (0.71 to 1.09)0.61 (0.53 to 0.87).03Tidal volume
Referência(s)