Inhaler Technique in Asthma: How Does It Relate to Patients' Preferences and Attitudes Toward Their Inhalers?

BACKGROUND: Correct inhaler technique can increase medication efficacy, reducing both dose and side effects. Patient preference for inhaler device has not been fully explored, and we hypothesized that if patients have a preference and can choose their inhaler, they might be more likely to use it correctly. Our aim was to determine the preferences, attitudes, and perceptions of patients with asthma toward their inhalers, and to evaluate whether any of these factors were related to inhalation technique. METHODS: Twenty-five patients with asthma (mean age 43.1 years) participated. Qualitative semi-structured interviews and quantitative patient satisfaction and preference questionnaires (PASAPQ) were used to explore patients' preferences, attitudes, and perceptions about their inhalers. Objective inhalation technique assessment was performed. Data were triangulated to identify characteristics that could indicate a relationship between inhaler technique, satisfaction, preference, and decision making. RESULTS: Themes from qualitative interviews were as follows: asthma inhalers and expectations; inhaler preference; characteristics of an ideal inhaler; perceived effectiveness of inhalers; and inhalers and patient decision making. PASAPQ scores indicated that all patients were at least "somewhat satisfied" with their inhalers, regardless of technique. Only 12% of inhalers were used correctly, despite pilot PASAPQ data suggesting that most patients were confident with their technique. The inhaler technique was unlikely to be related to satisfaction, perception of inhaler devices, or choice in device selection. Patients with correct inhaler technique were more aware of their asthma and expressed motivation to achieve optimal asthma control. CONCLUSIONS: The majority of the asthmatic patients did not use their inhaler(s) correctly, despite most having confidence in their technique. Patients attributed confidence in their inhaler technique to their belief that their inhaler was effective. Most patients had not been involved in decision making about which inhalation device to use. These findings highlight the lack of understanding of the important role of correct inhaler technique in asthma management.

Ventilation heterogeneity is associated with airway responsiveness in asthma but not COPD.

Airway hyperresponsiveness (AHR) occurs in both asthma and COPD. In older people with asthma, AHR is associated with increased acinar ventilation heterogeneity, but it is unknown if this association exists in COPD. Thirty one COPD and 19 age-matched asthmatic subjects had measures of spirometry, lung volumes, exhaled nitric oxide, ventilation heterogeneity, and methacholine challenge. Indices of acinar (Sacin) and conducting (Scond) airway ventilation heterogeneity were calculated from the multiple breath nitrogen washout. Predictors of AHR were then determined. In COPD, AHR was predicted by lower Sacin and lower FVC (model r(2)=0.35, p=0.001). In asthma, AHR was predicted by higher Sacin and higher residual volume (model r(2)=0.62, p<0.001). These findings suggest that airway responsiveness in COPD and asthma is determined by underlying disease-specific processes, rather than a common pattern of physiological abnormality.

Effect of methacholine on peripheral lung mechanics and ventilation heterogeneity in asthma.

The forced oscillation technique (FOT) and multiple-breath nitrogen washout (MBNW) are noninvasive tests that are potentially sensitive to peripheral airways, with MBNW indexes being especially sensitive to heterogeneous changes in ventilation. The objective was to study methacholine-induced changes in the lung periphery of asthmatic patients and determine how changes in FOT variables of respiratory system reactance (Xrs) and resistance (Rrs) and frequency dependence of resistance (Rrs5-Rrs19) can be linked to changes in ventilation heterogeneity. The contributions of air trapping and airway closure, as extreme forms of heterogeneity, were also investigated. Xrs5, Rrs5, Rrs19, Rrs5-Rrs19, and inspiratory capacity (IC) were calculated from the FOT. Ventilation heterogeneity in acinar and conducting airways, and trapped gas (percent volume of trapped gas at functional residual capacity/vital capacity), were calculated from the MBNW. Measurements were repeated following methacholine. Methacholine-induced airway closure (percent change in forced vital capacity) and hyperinflation (change in IC) were also recorded. In 40 mild to moderate asthmatic patients, increase in Xrs5 after methacholine was predicted by increases in ventilation heterogeneity in acinar airways and forced vital capacity (r(2) = 0.37, P < 0.001), but had no correlation with ventilation heterogeneity in conducting airway increase or IC decrease. Increases in Rrs5 and Rrs5-Rrs19 after methacholine were not correlated with increases in ventilation heterogeneity, trapped gas, hyperinflation, or airway closure. Increased reactance in asthmatic patients after methacholine was indicative of heterogeneous changes in the lung periphery and airway closure. By contrast, increases in resistance and frequency dependence of resistance were not related to ventilation heterogeneity or airway closure and were more indicative of changes in central airway caliber than of heterogeneity.

The role of the small airways in the clinical expression of asthma in adults.

BACKGROUND: The clinical relevance of increased ventilation heterogeneity, a marker of small-airways disease, in asthmatic patients is unclear. Ventilation heterogeneity is an independent determinant of airway hyperresponsiveness (AHR), improves with bronchodilators and inhaled corticosteroids (ICSs), and worsens during exacerbations, but its relationship to asthma control is unknown. OBJECTIVE: We sought to determine the association between ventilation heterogeneity and current asthma control before and after ICS treatment. METHODS: Adult subjects with asthma had lung function and asthma control (5-item Asthma Control Questionnaire [ACQ-5 score] ≥1.5 = poorly controlled, ACQ-5 score ≤0.75 = well controlled) measured at baseline. A subgroup with AHR had repeat measurements after 3 months of high-dose ICS treatment. The indices of ventilation heterogeneity in the regions of the lung where gas transport occurs predominantly through convection (ventilation heterogeneity in convection-dependent airways [Scond]) and through diffusion (ventilation heterogeneity in diffusion-dependent airways [Sacin]) were derived by using the multiple-breath nitrogen washout technique. RESULTS: At baseline (n = 105), subjects with poorly controlled asthma had worse FEV(1), fraction of exhaled nitric oxide measured at 200 mL/s (Feno), Scond, and Sacin values. In the treatment group (n = 50) spirometric, Feno, residual volume (RV)/total lung capacity (TLC), AHR, and Scond values significantly improved. Asthma control also improved (mean ACQ-5 score, 1.3-0.7; P < .0001). The change in ACQ-5 score correlated with changes in Feno (r(s) = 0.31, P = .03), Sacin (r(s) = 0.32, P = .02), and Scond (r(s) = 0.41, P = .003) values. The independent predictors of a change in asthma control were changes in Scond and Sacin values (model r(2) = 0.20, P = .005). CONCLUSIONS: Current asthma control is associated with markers of small-airways disease. Improvements in ventilation heterogeneity with anti-inflammatory therapy are associated with improvements in symptoms. Sensitive measures of small-airway function might be useful in monitoring the response to therapy in asthmatic subjects.

Predictors of airway hyperresponsiveness differ between old and young patients with asthma.

BACKGROUND: Age-related increases in morbidity and mortality due to asthma may be due to changes in pathophysiology as patients with asthma get older. There is limited knowledge about the effects of age on the predictors of airway hyperresponsiveness (AHR), a key feature of asthma. The aim of this study was to determine if the pathophysiologic predictors of AHR, including inflammation, ventilation heterogeneity, and airway closure, differed between young and old patients with asthma. METHODS: Sixty-one young (18-46 years) and 43 old (50-80 years) patients with asthma had lung function, lung volumes, fraction of exhaled nitric oxide, ventilation heterogeneity, and airway responsiveness to methacholine measured. Airway response to methacholine was measured by the dose-response slope, as the percent fall in FEV(1) per micromole of methacholine. Indices of ventilation heterogeneity were calculated for convection-dependent and diffusion-dependent airways. RESULTS: In young patients with asthma, the independent predictors of AHR were convection-dependent ventilation heterogeneity, exhaled nitric oxide, and % predicted FEV(1)/FVC (model r(2) = 0.51, P < .0001). In old patients with asthma, the independent predictors of airway responsiveness were % predicted residual volume, diffusion-dependent ventilation heterogeneity, and % predicted FEV(1) (model r(2) = 0.57, P < .0001). CONCLUSIONS: In old patients with asthma, AHR is predicted by gas trapping and ventilation heterogeneity in peripheral, diffusion-dependent airways. In the young, it is predicted by ventilation heterogeneity in less peripheral conducting airways and by inflammation. These findings suggest that there are differences in the pathophysiologic determinants of AHR between young and old patients with asthma.

Obesity is a determinant of asthma control independent of inflammation and lung mechanics.

BACKGROUND: It is unclear why obesity is associated with worse asthma control. We hypothesized that (1) obesity affects asthma control independent of spirometry, airway inflammation, and airway hyperresponsiveness (AHR) and (2) residual symptoms after resolution of inflammation are due to obesity-related changes in lung mechanics. METHODS: Forty-nine subjects with asthma underwent the following tests, before and after 3 months of high-dose inhaled corticosteroid (ICS) treatment: five-item asthma control questionnaire (ACQ-5), spirometry, fraction of exhaled nitric oxide (Feno), methacholine challenge, and the forced oscillation technique, which allows for the calculation of respiratory system resistance (Rrs) and respiratory system reactance (Xrs) as indicators of airway caliber and elastic load, respectively. The effects of treatment were assessed by BMI group (18.5-24.9, 25-29.9, and ≥ 30 kg/m²) using analysis of variance. Multiple regression analyses determined the independent predictors of ACQ-5 results. RESULTS: At baseline, the independent predictors of ACQ-5 results were FEV(1), Feno, and BMI (model r² = 0.38, P < .001). After treatment, asthma control, spirometry, airway inflammation, and AHR improved similarly across BMI groups. The independent predictors of ACQ-5 results after treatment were Rrs and BMI (model r² = 0.42, P < .001). CONCLUSIONS: BMI is a determinant of asthma control independent of airway inflammation, lung function, and AHR. After ICS treatment, BMI again predicts ACQ-5 results, but independent of obesity-related changes in lung mechanics.

Ventilation heterogeneity is a major determinant of airway hyperresponsiveness in asthma, independent of airway inflammation.

BACKGROUND: Airway hyperresponsiveness is the ability of airways to narrow excessively in response to inhaled stimuli and is a key feature of asthma. Airway inflammation and ventilation heterogeneity have been separately shown to be associated with airway hyperresponsiveness. A study was undertaken to establish whether ventilation heterogeneity is associated with airway hyperresponsiveness independently of airway inflammation in subjects with asthma and to determine the effect of inhaled corticosteroids on this relationship. METHODS: Airway inflammation was measured in 40 subjects with asthma by exhaled nitric oxide, ventilation heterogeneity by multiple breath nitrogen washout and airway hyperresponsiveness by methacholine challenge. In 18 of these subjects with uncontrolled symptoms, measurements were repeated after 3 months of treatment with inhaled beclomethasone dipropionate. RESULTS: At baseline, airway hyperresponsiveness was independently predicted by airway inflammation (partial r2 = 0.20, p<0.001) and ventilation heterogeneity (partial r2 = 0.39, p<0.001). Inhaled corticosteroid treatment decreased airway inflammation (p = 0.002), ventilation heterogeneity (p = 0.009) and airway hyperresponsiveness (p<0.001). After treatment, ventilation heterogeneity was the sole predictor of airway hyperresponsiveness (r2 = 0.64, p<0.001). CONCLUSIONS: Baseline ventilation heterogeneity is a strong predictor of airway hyperresponsiveness, independent of airway inflammation in subjects with asthma. Its persistent relationship with airway hyperresponsiveness following anti-inflammatory treatment suggests that it is an important independent determinant of airway hyperresponsiveness. Normalisation of ventilation heterogeneity is therefore a potential goal of treatment that may lead to improved long-term outcomes.

Effects of methacholine on small airway function measured by forced oscillation technique and multiple breath nitrogen washout in normal subjects.

The multiple breath nitrogen washout (MBNW) can be analysed to produce the parameters Scond and Sacin as measures of ventilation heterogeneity in conductive and acinar airways, respectively. The derivation of these parameters is based on a model of pulmonary ventilation and results of similar modelling suggest that respiratory system conductance (Grs) measured by forced oscillation technique (FOT) is also sensitive to heterogeneity and to airway closure. Therefore, Scond, the volume of gas trapping at FRC (VtrappedFRC) and Grs may be inter-related parameters. These relationships were examined in 12 normals under baseline and bronchoconstricted states. Specific Grs was measured at 5Hz (sGrs5=Grs5/FRC) and Scond, Sacin and VtrappedFRC by MBNW, before and after methacholine challenge. Scond was independently predicted by VtrappedFRC and FRC in a multivariate model (R2=0.68, p=0.002). Post methacholine challenge, Scond related only to VtrappedFRC (R2=0.79, p<0.0001). The absolute change in Scond induced by methacholine challenge were predicted by the changes in VtrappedFRC and sGrs5 in a multivariate model (R2=0.82, p=0.0002). Sacin was unrelated to VtrappedFRC and sGrs5 before and after methacholine challenge. In conclusion, Scond and sGrs5 are measurements that are sensitive to changes occurring to the function of peripheral conducting airways, in particular heterogeneity and airway closure, while Sacin and presumably heterogeneity in terminal airways, are independent of these. Scond is also related to lung size. We review the current state of knowledge of FOT and MBNW in obstructive lung diseases and discuss future research directions.

A single high dose of inhaled corticosteroids: a possible treatment of asthma exacerbations.

UNLABELLED: Recovery from an asthma exacerbation may take days or weeks even after the introduction of appropriate exacerbation therapy. However airway responsiveness and sputum eosinophils can be reduced within 6 hours by a single dose of inhaled corticosteroids. AIM: To determine if a single dose of 3200 microg of budesonide increases the rate of recovery from an asthma exacerbation. METHODS: Nineteen asthmatic subjects with an asthma exacerbation following withdrawal of inhaled corticosteroids were randomised to receive either usual care (doubling their dose of inhaled corticosteroids) plus placebo or usual care plus a single dose of 3200 microg of budesonide in a double-blind manner. Subjects monitored peak flow (PEF), symptoms, and beta agonist use daily for four weeks. The lowest PEF reading for each week was calculated as a percentage of the best peak flow value achieved in the recent past (PEF lowest % best). RESULTS: In the first week following exacerbation, PEF (lowest % best) was significantly greater in the budesonide group than in the placebo group (87.4 +/- 4.7 vs. 76.7 +/- 5.3; p = 0.029). However in the fourth week following exacerbation PEF was not significantly different (p = 0.728). The proportion of subjects who had a symptom free day during the first week was significantly higher in the budesonide group (p = 0.0012). CONCLUSION: A single high dose of inhaled corticosteroids added to usual exacerbation treatment might increase the rate of recovery from a mild exacerbation of asthma.