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

BACKGROUND: There 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. METHODS: Eighty 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. RESULTS: We 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. CONCLUSION: Abnormalities 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.

Normal limits for oscillometric bronchodilator responses and relationships with clinical factors.

INTRODUCTION: We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function. METHODS: Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance (R rs6 ) and reactance (X rs6 ) at 6 Hz, before and after inhalation of salbutamol 200 µg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease in R rs6 and 95th percentile increase in X rs6 in a healthy subgroup. RESULTS: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for ΔR rs6 was -1.38 cmH2O·s·L-1 (-30.0% or -1.42 Z-scores) and upper threshold for ΔX rs6 was 0.57 cmH2O·s·L-1 (1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, ΔX rs6 was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score. DISCUSSION: This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry.

Reduced lung elastic recoil and fixed airflow obstruction in asthma.

BACKGROUND AND OBJECTIVE: Fixed airflow obstruction (FAO) in asthma occurs despite optimal inhaled treatment and no smoking history, and remains a significant problem, particularly with increasing age and duration of asthma. Increased lung compliance and loss of lung elastic recoil has been observed in older people with asthma, but their link to FAO has not been established. We determined the relationship between abnormal lung elasticity and airflow obstruction in asthma. METHODS: Non-smoking asthmatic subjects aged >40 years, treated with 2 months of high-dose inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), had FAO measured by spirometry, and respiratory system resistance at 5 Hz (Rrs5 ) and respiratory system reactance at 5 Hz (Xrs5 ) measured by forced oscillation technique. Lung compliance (K) and elastic recoil (B/A) were calculated from pressure-volume curves measured by an oesophageal balloon. Linear correlations between K and B/A, and forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC), Rrs5 and Xrs5 were assessed. RESULTS: Eighteen subjects (11 males; mean ± SD age: 64 ± 8 years, asthma duration: 39 ± 22 years) had moderate FAO measured by spirometry ((mean ± SD z-score) post-bronchodilator FEV1 : -2.2 ± 0.5, FVC: -0.7 ± 1.0, FEV1 /FVC: -2.6 ± 0.7) and by increased Rrs5 (median (IQR) z-score) 2.7 (1.9 to 3.2) and decreased Xrs5 : -4.1(-2.4 to -7.3). Lung compliance (K) was increased in 9 of 18 subjects and lung elastic recoil (B/A) reduced in 5 of 18 subjects. FEV1 /FVC correlated negatively with K (rs = -0.60, P = 0.008) and Rrs5 correlated negatively with B/A (rs = -0.52, P = 0.026), independent of age. Xrs5 did not correlate with lung elasticity indices. CONCLUSION: Increased lung compliance and loss of elastic recoil relate to airflow obstruction in older non-smoking asthmatic subjects, independent of ageing. Thus, structural lung tissue changes may contribute to persistent, steroid-resistant airflow obstruction. CLINICAL TRIAL REGISTRATION: ACTRN126150000985583 at anzctr.org.au (UTN: U1111-1156-2795).

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

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Bronchodilator responsiveness of peripheral airways in smokers with normal spirometry.

BACKGROUND AND OBJECTIVE: Cigarette smoke exposure increases airway smooth muscle (ASM) contractility. Abnormalities in peripheral airway function in smokers with normal spirometry could be due to the effects of ASM tone. We aimed to determine the contribution of ASM tone to peripheral airway function in smokers with normal spirometry from the response to bronchodilator (BD). METHODS: Ventilation heterogeneity in peripheral conductive (Scond) and acinar (Sacin) airways were measured in 50 asymptomatic smokers and 20 never-smokers using multiple breath nitrogen washout, before and 20 min after inhalation of 200 µg salbutamol and 80 µg ipratropium bromide. Z-scores were calculated to define abnormality in Sacin and Scond. RESULTS: Nineteen smokers had abnormal Sacin, and 12 had abnormal Scond; 7 had abnormalities in both. After BD, Sacin improved in smokers with normal Sacin (6.5 ± 15.9%, P = 0.02), smokers with abnormal Sacin (9.2 ± 16.9%, P = 0.03) and in control subjects (11.7 ± 18.2%, P = 0.01), with no differences in improvements between groups. Sacin remained abnormal in 15/19 smokers and their post-BD values correlated with smoking exposure (r = 0.53, P = 0.02). After BD, Scond improved in smokers with abnormal Scond (28.3 ± 15.9%, P = 0.002) and normalized in 9/12 subjects, but not in those with normal Scond (0.25 ± 32.7%, P = 0.44) or control subjects (-1.7 ± 21.2%, P = 0.64). CONCLUSION: In smokers with normal spirometry, abnormal conductive airway function could be attributed to increased bronchomotor tone. In contrast, bronchomotor tone in acinar airways is unaffected by smoking and functional abnormality. There may be different causal mechanisms underlying acinar and conductive airway abnormalities in smokers with normal spirometry.