Design of Dry Powder Inhalers: 2. The Impact of Suboptimal Peak Inspiratory Flow Rates on Bronchodilation in Patients with Obstructive Lung Diseases.

Abstract

Background: Suboptimal peak inspiratory flow rate (sPIFR) has been proposed as a biomarker of disease progression in people with chronic obstructive pulmonary disease (COPD). Furthermore, sPIFR has been claimed to result in poor drug delivery, which in turn leads to poor clinical outcomes with passive dry powder inhalers (DPIs).

Results: Breathing studies suggest that most patients with COPD-including those with severe disease or experiencing an acute pulmonary exacerbation-can generate a pressure drop of at least 1.0 kPa. Across the 1.0-6.0 kPa range, variations in mean total lung dose of inhaled bronchodilators delivered with passive DPIs are modest: typically, no > 3-fold, and only 1.1 to 1.4-fold for most lactose blend-based products. Due to their large therapeutic indices, inhaled bronchodilators are formulated on the plateau of the dose-response curve, where comparable bronchodilation is typically achieved across a 2- to 4-fold dose range. Head-to-head comparisons of active delivery devices with passive DPIs show no differences in bronchodilation for the same drug, even in patients with sPIFR.

Conclusions: There is no compelling evidence to support the assertion that sPIFR with inhaled bronchodilators in asthma and COPD patients leads to inadequate drug delivery that results in marked decreases in lung function. On the contrary, the variations in PIFR typically observed with inhaled bronchodilators lead to consistent bronchodilation across a range of PIFR. Reductions in forced expiratory volume in one second with disease progression reflect reduced responsiveness to bronchodilators, not impaired drug delivery due to sPIFR. Options exist to dramatically improve lung targeting and dose consistency with inhaled medicines. These options are particularly valuable for treatments where the drug has a narrow therapeutic index or a high cost of goods.