Peripheral Airway Dysfunction Research Articles

Effect of somatotypes on lung volumes, capacities and respiratory impedance: A pilot study.

The current morphological condition of an individual is described by a somatotype, which is a three-number scale. The endomorph, mesomorph and ectomorph components are presented in the same sequence, and each number corresponds to one of the three basic components of body composition. We recruited 50 healthy male subjects with a mean age of 24.10 ± 4.55 yrs. Somatotype was determined by the Heath and Carter method. Impulse oscillometry was performed followed by spirometry according to the European Respiratory Society (ERS) or American Thoracic Society (ATS) guidelines. Resistance at 5 Hz (R5) %pred, R20%pred, R5-R20, X5%pred, X20, area of reactance (Ax) and resonant frequency (Fres) were obtained by doing impulse oscillometry. Slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio and maximum mid-expiratory flow (MMEF) were assessed by doing spirometry. Endomorphs (0.05 (0.00-0.09) vs 0.01 (0.00-0.04); P < 0.0001) and mesomorphs (0.04 (0.000.09) vs 0.01 (0.00-0.04); P = 0.002) had significantly higher R5-R20 than ectomorphs. Similarly, endomorphs (0.32 (0.07-0.82) vs 0.15 (0.08-0.35); P = 0.001) and mesomorphs (0.28 (0.17-0.64) vs 0.15 (0.08-0.35); P = 0.015) also showed significantly higher Ax than ectomorphs, Fres of endomorphs (15.37 (8.43-21.85) vs 10.08 (8.94-14.30); P < 0.0001) and mesomorphs (14.32 (10.24-20.86) vs 10.08 (8.94-14.30); P < 0.0001) were significantly high than ectomorphs. Moreover, spirometric measures reveal significant variation in which mesomorphs had significantly higher values of % predicted of FVC than ectomorphs (92.49 ± 7.211 vs 83.86 ± 7.861; P = 0.042) and the ratio of FEV1 to FVC was significantly higher in ectomorphs than in endomorphs (89.00 ± 5.80 vs 85.04 ± 5.73; P = 0.03). Peripheral airway dysfunction was observed in endomorphs and mesomorphs as compared to ectomorphs. Mesomorphs had a relatively higher FVC that may be due to their greater muscular strength.

Impulse oscillometry for the evaluation and management of pediatric asthma

Asthma is the most common chronic disease during childhood. While most of characteristic structural changes in asthma have been identified in the large airways, there is a growing recognition of peripheral airway dysfunction as a crucial factor in the development of asthma. This dysfunction is a defining feature in adults with persistent asthma. However, little is known about the contribution of small airway impairment in children with asthma due to the relatively low sensitivity of conventional lung function tests, such as spirometry. Recently, new diagnostic tools that are sensitive to both large and small airway function and inflammation have been introduced in clinical practice. The most widely studied of these tools in preschool and school-aged children is impulse oscillometry (IOS). This review addresses the latest findings on the usefulness of IOS in identifying small airway dysfunction, predicting the risk of uncontrolled asthma, and ultimately improving the diagnosis and management of asthma in children.

Peripheral airway dysfunction in prematurity-associated obstructive lung disease identified by oscillometry.

Mechanisms underlying lung dysfunction after preterm birth are poorly understood. Studying phenotypes of prematurity-associated lung disease may aid understanding of underlying mechanisms. Preterm-born children with and without lung dysfunction and term controls were assessed using oscillometry before and after exercise, and after postexercise bronchodilation. Preterm-born children, born at gestation of 34 weeks or less, were classified into those with prematurity-associated obstructive lung disease (POLD; FEV1 < LLN, FEV1 /FVC < LLN), prematurity-associated preserved ratio of impaired spirometry (pPRISm; FEV1 < LLN, FEV1 /FVC ≥ LLN) and compared to preterm (FEV1 ≥ LLN) and term controls (%predicted FEV1 > 90%). All children underwent cardiopulmonary exercise, and oscillometry assessment at baseline, postexercise, and after postexercise bronchodilator administration. From 241 participants aged 7-12 years, complete data were available from 179: 15 children with POLD and 11 with pPRISm were compared with 93 preterm and 60 term controls. POLD group, when compared to both control groups, had impaired impedance, greater resistance, more negative (greater magnitude) reactance at low frequencies, and also had decreased compliance. pPRISm group demonstrated impaired reactance and compliance compared to term controls. No differences were noted between the preterm and term controls. Exercise had little impact on oscillometry values, but children with POLD had greatest improvements after postexercise bronchodilator administration, with decreased resistance and decreased magnitude of reactance, particularly at low frequencies. Preterm-born children with obstructive airway disease had the greatest oscillometry impairments and the largest improvements after postexercise bronchodilator compared to control groups. Oscillometry can potentially be used to identify preterm-born children with lung disease to institute treatment.

Clinical impact of obesity on oscillometry lung mechanics in adults with asthma

BackgroundIn the year 2035, projections have estimated that 5% of the Scottish population will be morbidly obese defined as a body mass index (BMI) greater than or equal to 40 kg/m2. Airway oscillometry is an effort-independent test akin to bronchial sonar which measures resistance and compliance. ObjectiveTo evaluate the impact of obesity on lung mechanics using oscillometry. MethodsClinical data for 188 patients with respiratory physician–diagnosed moderate-to-severe asthma were retrospectively collected and analyzed. ResultsObesity (BMI 30-39.9 kg/m2) and morbid obesity (BMI ≥ 40 kg/m2) were associated with a significantly worse heterogeneity of peripheral resistance between 5 Hz and 20 Hz and peripheral compliance as low-frequency reactance at 5 Hz and area under the reactance curve, as compared with normal weight (BMI 18.5-24.9 kg/m2). Cluster analysis incorporating oscillometry identified a patient cohort who was older, obese, and female with combined impairment of spirometry and oscillometry coupled with more frequent severe exacerbations. ConclusionObesity is associated with worse peripheral airway dysfunction in moderate-to-severe asthma, including a patient cluster who was older, obese, and female with more frequent exacerbations.

Early Life Risk Factors for Small Airways Dysfunction Across Childhood and Adolescence as Measured by Impulse Oscillometry

Early life risk-factors are important to lung health across the lifespan. Increased airway resistance (R) as assessed by R5-R20 Hz using Impulse Oscillometry (IOS) is a non-invasive assessment of peripheral airway dysfunction. We hypothesized that early life exposures and risk factors in participants in the Childhood Origins of ASThma (COAST) birth-cohort study will influence R5-R20 across childhood and adolescence.

Peripheral Airway Dysfunction in Obesity and Obese Asthma

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 ± 6.6kg/m2 in control subjects and 47.2 ± 8.2kg/m2 in people with asthma). Most participants had significant changes in peripheral airway impedance in response to methacholine: in control subjects, resistance at 5Hz measured by oscillometry increased by 45%± 27%and area under the reactance curve (AX) by 268%± 236%in response to 16mg/mL methacholine; in people with asthma, resistance at 5Hz 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, 9.9-23.4cm H2O/L) and more concordant bronchoconstriction in central and peripheral airways; the other with high reactance (baseline AX, 46.7; interquartile range, 23.2-53.7cm 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.

Small airways dysfunction is associated with increased exacerbations in patients with asthma.

There is a poor understanding of why some patients with asthma experience recurrent exacerbations despite high levels of treatment. We compared measurements of peripheral ventilation heterogeneity and respiratory system mechanics in participants with asthma who were differentiated according to exacerbation history, to ascertain whether peripheral airway dysfunction was related to exacerbations. Three asthmatic groups: "stable" (no exacerbations for >12 mo, n = 18), "exacerbation-prone" (≥1 exacerbation requiring systemic corticosteroids within the last 12 mo, but stable for ≥1-mo, n = 9), and "treated-exacerbation" (exacerbation requiring systemic corticosteroids within the last 1 mo, n = 12) were studied. All participants were current nonsmokers with <10 pack yr smoking history. Spirometry, static lung volumes, ventilation heterogeneity from multibreath nitrogen washout (MBNW), and respiratory system mechanics from oscillometry were measured. The exacerbation-prone group compared with the stable group had slightly worse spirometry [forced expired volume in 1 s or FEV1 z-score -3.58(1.13) vs. -2.32(1.06), P = 0.03]; however, acinar ventilation heterogeneity [Sacin z-score 7.43(8.59) vs. 3.63(3.88), P = 0.006] and respiratory system reactance [Xrs cmH2O·s·L-1 -2.74(3.82) vs. -1.32(1.94), P = 0.01] were much worse in this group. The treated-exacerbation group had worse spirometry but similar small airway function, compared with the stable group. Patients with asthma who exacerbate have worse small airway function as evidenced by increases in Sacin measured by MBNW and ΔXrs from oscillometry, both markers of small airway dysfunction, compared with those that do not.NEW & NOTEWORTHY This study assessed the relationship between peripheral airway function, measured by multiple breath nitrogen washout and oscillometry impedance, and exacerbation history. We found that those with a history of exacerbation in the last year had worse peripheral airway function, whereas those recently treated for an asthma exacerbation had peripheral airway function that was comparable to the stable group. These findings implicate active peripheral airway dysfunction in the pathophysiology of an asthma exacerbation.

Methods for diagnosing dysfunction of small airways and uniformity of lung ventilation: their use after a novel coronavirus infection

In this lecture, we discussed methods and approaches to the diagnosis of small airways dysfunction, such as multiple breath nitrogen washout test, impulse oscillometry, as well as the calculation of poorly communicating fraction (PCF) as the ratio of total lung capacity to alveolar volume. The detection of the small airways dysfunction with the help of the diagnostic tools listed above makes it possible to establish functional disorders of the respiratory system in the early stages of bronchopulmonary diseases, when the results of traditional pulmonary functional tests remain within normal values. Thus, a well-standardized and the most accessible method for detecting the peripheral airways dysfunction is body plethysmography, which is used to diagnose the presence of “air trappings”. However, in the early stages of bronchopulmonary diseases, the possibilities of this method are limited. The lecture focuses primarily on the results of our own researches which were performed on patients who have suffered from a novel coronavirus infection complicated by viral pneumonia. Spirometry, body plethysmography, diffusion test, impulse oscillometry, multiple breath nitrogen washout test were conducted, and PCF index was calculated in all patients included in this analysis. The description of the PCF index, the method of its calculation, the range of normal values, as well as the possibilities of application in clinical practice are given for the first time in the Russian literature. The approaches to assessing the dysfunction of the small airways described in the lecture are not widely used at present, however, we hope that the knowledge that is currently being applied in scientific laboratories will gradually be introduced into routine clinical practice.

Relationship between concavity of the flow-volume loop and small airway measures in smokers with normal spirometry

BackgroundThere is increasing evidence of small airway abnormalities in smokers despite normal spirometry. The concavity in the descending limb of the maximum expiratory flow curve (MEFV) is a recognised feature of obstruction and can provide information beyond FEV1, and potentially early smoking-related damage. We aimed to evaluate concavity measures compared to known small airway measurements.MethodsEighty smokers with normal spirometry had small airway function assessed: multiple breath nitrogen washout (MBNW) from which ventilation heterogeneity in the diffusion-dependent acinar (Sacin) and convection-dependent conductive (Scond) airways were assessed, and impulse oscillometry system (IOS) from which respiratory resistance and reactance at 5 Hz (R5 and X5) were measured. Concavity measures were calculated from the MEFV, partitioned into global and peripheral concavity.ResultsWe found abnormal peripheral and global concavity as well as acinar ventilation heterogeneity are common in “normal” smokers. Concavity measures were not related to either MBNW or IOS measurements.ConclusionAbnormalities in concavity indices and MBNW or oscillometry parameters are common in smokers despite normal spirometry. However, these measures likely reflect different mechanisms of peripheral airway dysfunction.

Prevalence of pneumoconiosis and spirometric findings in underground mining workers in Cundinamarca, Colombia

Introduction: Coal worker’s pneumoconiosis is caused by the inhalation of coal dust and its accumulation in the lungs after several years of exposure.Objective: To determine the prevalence of pneumoconiosis in underground mining workers exposed to coal dust in Cundinamarca, Colombia, and its association with their spirometry results and respiratory symptoms.Materials and methods: Cross-sectional study conducted on 215 workers who were administered a questionnaire on respiratory symptoms. For each worker a chest radiograph was taken according to the criteria of the International Labor Organization. Information on the workers’ socio-demographic characteristics, smoking habits, and spirometry results was included.Results: The average age was 45.5 ± 9.4 years and the average length of employment was 21.7±10.0 years. Expectoration was the symptom most frequently reported (73.5%). Regarding spirometry results, a normal pattern was observed in 89.8% of the sample, while obstructive and restrictive patterns were found in 5.1% and 3.7% of the subjects, and 0.5% had a peripheral airways dysfunction pattern. The prevalence of pneumoconiosis was 42.33%. FEV1/FVC ratio (81.75 vs. 83.74, p=0.045) and FF25-75% (84.96 vs. 91.95, p&lt;0.001) mean values were significantly lower in workers with pneumoconiosis.Conclusion: Pneumoconiosis was highly prevalent in the study population and its diagnosis was associated with spirometry results (FEV1/FVC and FEF25.75%); bearing in mind that currently there are not effective treatments for this disease, it is necessary to implement control and prevention strategies aimed at reducing occupational exposure to coal dust and, this way, prevent its occurrence.

First case of acute respiratory distress syndrome and alimentary tract hemorrhage following mass ingestion of methylisothiazolinone

The frequency of methylisothiazolinone (MIT)-related health concerns regarding allergic contact dermatitis with a spongiotic reaction pattern and restrictive lung function indicating peripheral airway dysfunction caused by the use of humidifier disinfectant is increasingly rising. There is a limited number of evidences supporting the environmentally acute and mass exposure to MIT resulting in acute respiratory distress syndrome (ARDS). Here, we report the first case of ARDS and alimentary tract hemorrhage following mass ingestion of methylisothiazolinone.

Peripheral small airway dysfunction differences between idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Objective: To investigate the peripheral small airway dysfunction differences between idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Impulse oscillmetory system testing (IOS) and pulmonary function testing (PFT) were performed in IPAH and CTEPH patients and 30 healthy control group. We also carried out a subgroup analysis depending on their medical history of airway diseases. Results: We included 42 IPAH and 47 CTEPH patients (with or without airways disease: 8 vs. 34 and 17 vs. 34, respectively). Compared with CTEPH patients, IPAH patients were younger but had more serious pulmonary vessel resistance and mean pulmonary arterial resistance. Compared with IPAH patients, CTEPH patients had significant impaired peripheral small airway dysfunction with decreased of MEF(50) (% pred), MMEF(75/25) evaluated by PFT and R5-R20, Δ R5-R20 and AX measured by IOS [10.6(2.0, 33.0) vs. 2.5(-5.0, 16.5); 22.1(14.0, 32.6) vs. 15.5 (7.0, 23.2); 7.64(4, 18.6) vs. 6(3, 11) respectively, all P<0.05]. Subgroup analysis revealed there were no significant peripheral small dysfunction differences in IPAH patients with or without airway diseases. CTEPH patients had a higher proportion of airway diseases and more serious peripheral dysfunction than IPAH patients with airway diseases. Compared with control healthy group, peripheral airway dysfunction was more obvious even in IPAH and CTEPH patients without airway diseases. Conclusion: Compared with IPAH, CTEPH patients were older, but had better hemodynamics and a higher proportion of airway diseases. The peripheral airway dysfunction were more serious in CTEPH patients without airway diseases than IPAH patients without airway diseases and healthy controls group.

Particles in exhaled air (PExA): non-invasive phenotyping of small airways disease in adult asthma

Rationale: Asthma is often characterised by inflammation, damage and dysfunction of the small airways, but no standardised biomarkers are available. Objectives: Using a novel approach—particles in exhaled air (PExA)—we sought to (a) sample and analyse abundant protein biomarkers: surfactant protein A (SPA) and albumin in adult asthmatic and healthy patients and (b) relate protein concentrations with physiological markers using phenotyping. Methods: 83 adult asthmatics and 21 healthy volunteers were recruited from a discovery cohort in Leicester, UK, and 32 adult asthmatics as replication cohort from Sweden. Markers of airways closure/small airways dysfunction were evaluated using forced vital capacity, impulse oscillometry and multiple breath washout. SPA/albumin from PEx (PExA sample) were analysed using ELISA and corrected for acquired particle mass. Topological data analysis (TDA) was applied to small airway physiology and PExA protein data to identify phenotypes. Results: PExA manoeuvres were feasible, including severe asthmatic subjects. TDA identified a clinically important phenotype of asthmatic patients with multiple physiological markers of peripheral airway dysfunction, and significantly lower levels of both SPA and albumin. Conclusion: We report that the PExA method is feasible across the spectrum of asthma severity and could be used to identify small airway disease phenotypes.

Sleep Disturbances in COPD are Associated with Heterogeneity of Airway Obstruction

Individuals with Chronic Obstructive Pulmonary Disease (COPD) experience sleep disturbances due to the impact of respiratory symptoms on sleep quality. We explored whether sleep disturbances in COPD are linked to heterogeneity of airway constriction.The impact of breathing problems on sleep quality was measured in consecutive COPD outpatients with the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Impulse oscillometry technique (IOS) was employed to assess heterogeneity of airway constriction. Subjects with a previous or concomitant diagnosis of asthma or obstructive sleep apnea (OSA) were excluded.Fifty COPD subjects (M/F 40/10; age: 71 ± 8 yrs, Body Mass Index (BMI): 26.2 ± 4.7 kg/m2, Forced Expiratory Volume in the first second (FEV1): 65 ± 25% predicted; mean ± SD) were enrolled. The mean CASIS score was 36 ± 3.3, and the R5–R20 value was 0.2 ± 0.15 kPa s L−1. The CASIS score was significantly higher in subjects with increased R5–R20 (>0.07 kPa s L−1) (39 ± 24; p = 0.02) compared to normal R5–R20 (21 ± 17). When subjects were categorized on the basis of lung function in severely versus non severely obstructed (FEV1 ≤ or >50% predicted) or air trappers versus non air trappers (Residual Volume, RV ≥ or <120% predicted) the CASIS score remained unchanged (for FEV1: 37 ± 23 versus 33 ± 25, respectively, p = 0.61; for RV: 30 ± 20 versus 40 ± 23, p = 0.16).Sleep disturbances due to COPD symptoms are associated with heterogeneity of airway constriction, possibly reflecting peripheral airway dysfunction.

Clinical phenotypes of bronchial hyperresponsiveness in school-aged children

BackgroundBronchial hyperresponsiveness (BHR), one of the key features of asthma, has a diverse natural course in school-aged children, but studies on BHR phenotypes are lacking. ObjectiveTo classify BHR phenotypes according to onset age and persistence in children and investigate the characteristics and factors associated with each phenotype in a longitudinal study. MethodsThis study analyzed 1,305 elementary school children from the Children's Health and Environmental Research (CHEER) study, a 4-year, prospective, follow-up study with 2-year intervals starting at a mean age of 7 years. Total serum IgE levels and blood eosinophil counts were measured, and allergy workup, including methacholine challenge tests with the International Study of Asthma and Allergies in Childhood questionnaire, was performed at each survey. ResultsThe 4 BHR phenotypes were classified as non-BHR (n = 942 [72.2%]), early-onset transient BHR (n = 201 [15.4%]), late-onset BHR (n = 87 [6.7%]), and early-onset persistent BHR (n = 75 [5.7%]). Early-onset persistent BHR is characterized by an increased eosinophil count, total serum IgE level, sensitization rate, decreased lung function, and increased risk of newly diagnosed asthma during follow-up (adjusted odds ratio, 3.89; 95% confidence interval, 1.70-8.88). The 2 early-onset phenotypes were associated with peripheral airway dysfunction. The late-onset BHR phenotype was related to increased risks of allergic rhinitis symptoms at baseline and later sensitization against inhalant allergens. ConclusionThe early-onset persistent BHR phenotype in school-aged children is associated with high atopic burden and increased risk of newly diagnosed asthma, whereas the late-onset BHR phenotype related with later sensitization and allergic rhinitis symptoms. Diverse BHR phenotypes in children have specific characteristics that require targeted follow-ups.

Effects of bronchodilation on biomarkers of peripheral airway inflammation in COPD

Peripheral airway inflammation and dysfunction are key elements in the pathogenesis of COPD. The exhaled alveolar fraction of nitric oxide (CANO) is an indirect biomarker of lung peripheral inflammation. We tested whether inhaled long-acting bronchodilators (LABA) can affect CANO and we evaluated correlations with lung mechanics in patients with COPD.Two-centre, randomised, double blind, crossover study including COPD patients with moderate-to-severe airflow obstruction. Following a pharmacological washout, multi-flow exhaled fraction of NO (FENO), plethysmography, lung diffusion (DLCO), single breath nitrogen washout test and dyspnoea were measured in a crossover manner at baseline and 30, 60 and 180 min following administration of salmeterol (Sal) or formoterol fumarate (FF). (ClinicalTrials.gov, number NCT01853787).Fort-five patients were enrolled (median age: 71.8 years; 84.4% males). At baseline, CANO correlated with airway resistances (r = 0.422), residual volume/total lung capacity (RV/TLC; r = 0.375), transfer factor (r= -0.463) and forced expiratory volume in 1 s (FEV1; r= -0.375, all P < 0.01). After LABA administration, we found a significant reduction of FENO that reached statistical significance at 180’; no difference was found between FF and S. Consistently, a significant reduction of CANO was documented at 60’ and 180’ compared to baseline for both FF and S (P < 0.01 and P < 0.05, respectively). Changes in CANO were correlated with changes in vital capacity (r=-44; P < 0.001) and RV/TLC (r = 0.56; P < 0.001), but not FEV1.In COPD, direct correlations were found between the levels of CANO and the magnitude of peripheral airway dysfunction. LABA reduced CANO levels. The reduction was associated with improvement in functional parameters reflecting air trapping.

Small airways dysfunction: the link between allergic rhinitis and allergic asthma.

Abnormal airway reactivity and overproduction of nitric oxide (NO) occurring in small airways have been found in asthma. If the "one airway, one disease" concept is consistent, such dysfunctions should also be detected in the peripheral airways of patients suffering from allergic rhinitis.We investigated whether peripheral airway reactivity and NO overproduction could be documented in distal airways in patients with allergic rhinitis. Exhaled NO fraction (FeNO) and the slope (S) of phase III of the single-breath washout test (SBWT) of helium (He) and sulfur hexafluoride (SF6) were measured in 31 patients with allergic asthma, 23 allergic rhinitis patients and 24 controls, before and after sputum induction. SBWT is sensitive to airway calibre change occurring in the lung periphery.The FeNO decrease was more significant in asthma and rhinitis than in controls (-55.1% and -50.0%, respectively, versus -40.8%) (p=0.007 and p=0.029, respectively). SSF6 and SHe increased in all groups. Change in SHe (ΔSHe) > ΔSSF6 was observed in rhinitis (p=0.004) and asthma (p<0.001), whereas ΔSSF6 = ΔSHe in controls (p=0.431).This study provides evidence of peripheral airway dysfunction in patients with allergic rhinitis quite similar to that described in asthma. Furthermore, a large proportion of the increased NO production reported in allergic rhinitis appears to originate in the peripheral airways.

Assessment of proximal and peripheral airway dysfunction by computed tomography and respiratory impedance in asthma and COPD patients with fixed airflow obstruction.

OBJECTIVE:To ascertain: (i) if elderly patients with fixed airflow obstruction (FAO) due to asthma and chronic obstructive pulmonary disease (COPD) have distinct airway morphologic and physiologic changes; (ii) the correlation between the morphology of proximal/peripheral airways and respiratory impedance.METHODS:Twenty-five asthma cases with FAO and 22 COPD patients were enrolled. High-resolution computed tomography was used to measure the wall area (WA) and lumen area (LA) of the proximal airway at the apical segmental bronchus of the right upper lobe (RB1) adjusted by body surface area (BSA) and bronchial wall thickening (BWTr) of the peripheral airways and extent of expiratory air trapping (ATexp). Respiratory impedance included resistance at 5 Hz (R5) and 20 Hz (R20) and resonant frequency (Fres). Total lung capacity (TLC) and residual volume (RV) were measured.RESULTS:Asthma patients had smaller RB1-LA/BSA than COPD patients (10.5 ± 3.4 vs. 13.3 ± 5.0 mm2/m2, P = 0.037). R5(5.5 ± 2.0 vs. 3.4 ± 1.0 cmH2O/L/s, P = 0.02) and R20(4.2 ± 1.7 vs. 2.6 ± 0.7 cmH2O/L/s, P = 0.001) were higher in asthma cases. ATexp and BWTr were similar in both groups. Regression analysis in asthma showed that forced expiratory volume in one second (FEV1) and Fres were associated with RB1-WA/BSA (R2= 0.34, P = 0.005) and BWTr (0.5, 0.012), whereas RV/TLC was associated with ATexp (0.38, 0.001).CONCLUSIONS:Asthma patients with FAO had a smaller LA and higher resistance of the proximal airways than COPD patients. FEV1 and respiratory impedance correlated with airway morphology.

Peripheral airway dysfunction and relationship with symptoms in smokers with preserved spirometry.

Smokers develop respiratory symptoms and peripheral airway dysfunction even when spirometry is preserved. Multiple breath nitrogen washout (MBNW) and impulse oscillometry system (IOS) are potentially useful measures of peripheral airway function but they have not been compared in such subjects. We hypothesized that MBNW and IOS are jointly abnormal in smokers with normal spirometry and that these abnormalities relate to respiratory symptoms. Eighty smokers with normal spirometry completed a symptom questionnaire, had ventilation heterogeneity in diffusion (Sacin) and convection-dependent (Scond) airways and trapped gas volume at functional residual capacity as a percentage of vital capacity (%VtrFRC/VC) measured by MBNW. Respiratory resistance and reactance at 5 and 20 Hz were measured using IOS. Respiratory symptoms were reported in 55 (68%) subjects. Forty (50%) subjects had at least one abnormal MBNW parameter, predominantly in Sacin. Forty-one (51%) subjects had at least one abnormal IOS parameter, predominantly in resistance. Sixty-one (76%) subjects had an abnormality in either MBNW or IOS. Chronic bronchitis symptoms were associated with an increased Scond, while wheeze was associated with lower spirometry and an increased resistance. Abnormalities in MBNW and IOS parameters were unrelated to each other. Respiratory symptoms and peripheral airway dysfunction are common in smokers with normal spirometry. Symptoms of chronic bronchitis related to conductive airway abnormalities, while wheeze was related to spirometry and IOS. The clinical significance of abnormalities in peripheral airway function in smokers remains undetermined.

Peripheral ventilation heterogeneity determines the extent of bronchoconstriction in asthma.

In asthma, bronchoconstriction causes topographically heterogeneous airway narrowing, as measured by three-dimensional ventilation imaging. Computation modeling suggests that peripheral airway dysfunction is a potential determinant of acute airway narrowing measured by imaging. We hypothesized that the development of low-ventilation regions measured topographically by three-dimensional imaging after bronchoconstriction is predicted by peripheral airway function. Fourteen asthmatic subjects underwent ventilation single-photon-emission computed tomography/computed tomography scan imaging before and after methacholine challenge. One-liter breaths of Technegas were inhaled from functional residual capacity in upright posture before supine scanning. The lung regions with the lowest ventilation (Ventlow) were calculated using a thresholding method and expressed as a percentage of total ventilation (Venttotal). Multiple-breath nitrogen washout was used to measure diffusion-dependent and convection-dependent ventilation heterogeneity (Sacin and Scond, respectively) and lung clearance index (LCI), before and after challenge. Forced expiratory volume in 1 s (FEV1) was 87.6 ± 15.8% predicted, and seven subjects had airway hyperresponsiveness. Ventlow at baseline was unrelated to spirometry or multiple-breath nitrogen washout indices. Methacholine challenge decreased FEV1 by 23 ± 5% of baseline while Ventlow increased from 21.5 ± 2.3%Venttotal to 26.3 ± 6.7%Venttotal (P = 0.03). The change in Ventlow was predicted by baseline Sacin (rs = 0.60, P = 0.03) and by LCI (rs = 0.70, P = 0.006) but not by Scond (rs = 0.30, P = 0.30). The development of low-ventilation lung units in three-dimensional ventilation imaging is predicted by ventilation heterogeneity in diffusion-dependent airways. This relationship suggests that acinar ventilation heterogeneity in asthma may be of mechanistic importance in terms of bronchoconstriction and airway narrowing.NEW & NOTEWORTHY Using ventilation SPECT/CT imaging in asthmatics, we show induced bronchoconstriction leads to the development of areas of low ventilation. Furthermore, the relative volume of the low-ventilation regions was predicted by ventilation heterogeneity in diffusion-dependent acinar airways. This suggests that the pattern of regional airway narrowing in asthma is determined by acinar airway function.