Suboptimal Inspiratory Flow Rates With Passive Dry Powder Inhalers: Big Issue or Overstated Problem?

The maximum inspiratory pressure (MIP) that a subject can achieve through the mouthpiece of a “passive” dry powder inhaler (DPI) is driven chiefly by their inspiratory muscle strength (Clark, 2015). Muscle strength increases with age, peaking at about age 25, plateauing until about age 40, after which it steadily decreases. Males achieve greater MIP values than females, and increases in disease severity may further reduce MIP. When using DPIs, patients rarely inhale with maximal effort, instead achieving peak inspiratory pressures (PIP) that are about 40–80% of their MIP (Clark, 2015 and references therein). Based on these observations, current industry guidance is that passive DPIs are inherently flow rate dependent, and that young children and elderly patients may not be able to achieve the PIP or peak inspiratory flow rates (PIFR) necessary to effectively fluidize and disperse dry powders, especially during acute exacerbations (Laube et al., 2011). For patients with COPD, it has been suggested that: “If the PIFR is less than 60 L min the patient may not achieve optimal clinical benefit (with inhaled bronchodilators), and a different delivery system such as a metered dose or soft mist inhaler or nebulized therapy should be considered” (Mahler, 2017). Based on results of multiple breathing studies in COPD patients, it was further suggested that between 19 and 78% of stable outpatients, and 32–47% of in-patients prior to discharge after admission for an exacerbation, have a suboptimal PIFR <60 L min (Mahler et al., 2013; Mahler, 2017; Mahler, 2020). More recently, Mahler has taken the argument one step further, suggesting that PIFR be used as a therapeutic biomarker to guide delivery system selection, while dropping the optimal flow rate for high resistance DPIs to 30 L min (Mahler and Halpin, 2021). This opinion reviews the available literature regarding flow rate dependence of inhaled bronchodilators when administered with passive DPIs for the treatment of asthma and COPD.