Numerical simulation of the effect of inhalation parameters, gender, age and disease severity on the lung deposition of dry powder aerosol drugs emitted by Turbuhaler®, Breezhaler® and Genuair® in COPD patients.

The effect of breathing parameters on the airway deposition of the inhaled aerosols with known size was intensively studied in the literature. However, in the case of dry powder aerosol drugs both the quantity and quality of the particles emitted by the inhaler and inhaled by the patients is a complex function of the patient's breathing parameters, which in turn depend also on the disease severity and current status of the patient. The aim of this study was to evaluate the impact of breathing parameters, gender, age, symptoms and exacerbation history related disease severity (GOLD groups) of chronic obstructive pulmonary disease (COPD) patients on the lung dose of four different drugs emitted by three DPIs (dry powder inhalers). Breathing profiles of 47 COPD patients were recorded while they inhaled through Turbuhaler®, Breezhaler® and Genuair® inhalers. Patient specific emitted doses and particle size distributions were determined for Symbicort® Turbuhaler®, Onbrez® Breezhaler®, Seebri® Breezhaler® and Bretaris® Genuair® aerosol drugs. Airway deposition was quantified by a validated whole respiratory tract particle deposition model. Correlation analysis of the lung doses with breathing parameters through the devices and with standard spirometric parameters was performed. The effects of gender, age and degree of disease severity (GOLD groups) on the lung doses were also studied by statistical analysis. Mean values and distributions of the deposited lung doses proved to be both drug and device specific, yielding 24.2 (±7.8), 22.6 (±3.6), 34.2 (±4.8) and 23.9 (±5.4) % values for Symbicort®, Onbrez®, Seebri® and Bretaris®, respectively. Drugs with flow rate sensitive emitted dose and emitted particle size distribution exhibited higher intersubject variability of the lung doses. The degree of correlation of lung doses with breathing parameters through the devices was also drug specific. Correlation with flow rate was the strongest for Symbicort® Turbuhaler®. Longer breath-hold increased the lung dose of all the studied drugs. Correlations of lung dose with standard spirometric parameters was generally weaker than its correlation with the parameters measured when inhaling through the devices. Men had higher lung deposition than women, younger patients had higher deposition than older ones and patients with less severe disease higher doses than those with more severe COPD, but the differences were statistically significant only upon gender and only in case of Symbicort® and Seebri®. Patients with better inhalation parameters are likely to have higher lung deposition when inhaling a drug with emitted dose and particle size distribution sensitive to the inhalation flow rate. At the same time, patients with lower lung capacity show better deposition results when inhaling from inhalers emitting a more constant amount of drug and particles with more stable aerodynamic characteristics. A more powerful inhalation significantly increases the lung dose for the drug emitted by Turbuhaler®, while long breath-hold is likely to yield significantly higher deposition for drugs emitted by Breezhaler® and Genuair®. Lung doses of two different drugs dispensed in the same inhaler can be significantly different.

Establishment of relationships between native and inhalation device specific spirometric parameters as a step towards patient tailored inhalation device selection.

INTRODUCTION: Drug emission from DPIs is dependent on the inspiratory flow parameters through them, which are not directly measured by standard spirometry. Their estimation based on native spirometric data could help in choosing the appropriate device and optimizing the drug deposition. OBJECTIVES: The aim of this study was to survey patient preferences and to find correlations between breathing parameters of COPD patients through DPI devices and their baseline spirometric data, age, gender, disease severity and anthropometric characteristics. Another objective was to establish relationships between peak inspiratory flows (PIFdev) through Breezhaler®, Genuair® and Turbuhaler® inhalers and their determinants. METHODS: Breathing parameters of 49 patients with previously diagnosed COPD and currently using one of the above inhalers were recorded by normal spirometry and while inhaling through the selected DPIs. Statistical analysis of the measured data was completed. All specific data are provided as (mean ±â€¯standard deviation). RESULTS: More than 60% of the patients stated that their current device is the easiest to use. The means of the measured PIFdev values were 91.4 L/min, 77.1 L/min and 77.5 L/min for Breezhaler®, Genuair®, and Turbuhaler®, respectively. PIFdev values were significantly higher for males than for females, but differences upon age, BMI and disease severity group were not significant (at p = 0.05). Peak inspiratory flows through the inhalers (PIFdev) correlated best with their native spirometric counterparts (PIF) and linear PIFdev-PIF relationships could be determined (Breezhaler®: r = 0.60, p = 0.002, Genuair®: r = 0.55, p = 0.001, Turbuhaler®: r = 0.57, p = 0.002). Physical background of the deduced equations was also provided. CONCLUSIONS: Present correlations may be used to assess the success of inhalation of COPD patients through the studied devices and to choose the appropriate device for each patient. As a consequence, the amount of the drug emitted by the device can be optimized, the deposition efficiency within the lungs increased and the related therapeutic effect improved.

Variability of breath condensate pH may contribute to the better understanding of non-allergic seasonal respiratory diseases.

The seasonal variability of certain non-allergic respiratory diseases is not clearly understood. Analysis of the breath condensate, the liquid that can be collected by breathing into a cold tube, has been proposed to bring closer to the understanding of airway pathologies. It has been assumed, that (1) airway lining fluid was a stable body liquid and (2) the breath condensate samples were representative of the airway lining fluid. Research was focussed on the identification of biomarkers indicative of respiratory pathologies. Despite 30 years of extended investigations breath condensate analysis has not gained any clinical implementation so far. The pH of the condensate is the characteristic that can be determined with the highest reproducibility. The present paper shows, that contrary to the initial assumptions, breath condensate is not a representative of the airway lining fluid, and the airway lining fluid is not a stable body liquid. Condensate pH shows baseline variability and it is influenced by drinking and by the ambient temperature. The changes in condensate pH are linked to changes in airway lining fluid pH. The variability of airway lining fluid pH may explain seasonal incidence of certain non-allergic respiratory diseases such as the catching of a common cold and the increased incidence of COPD exacerbations and exercise-induced bronchoconstriction in cold periods.