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

It is easy to forget that just a few decades ago, delivery of drugs by inhalation was at the periphery of medicine, even for the treatment of respiratory diseases. Today, it would be almost unthinkable that a patient with asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis would not be taking some form of inhaled medication and, indeed, typically more than one daily (Anderson et al., 2022). While the dominant inhalation technology invented in mid-1950s for decades were metered dose inhalers (MDIs), due to concerns over the environmental impact of propellants that provide the energy for the production of the aerosols, the pharmaceutical industry put a massive effort into reformulating drugs as dry powder inhalers (DPIs), particularly since the Montreal agreement signed in 1987 (Stein and Thiel, 2016). Instead of propellants, “passive” DPIs utilize the energy of the patients’ inspiratory effort to pull the drug powder formulation out of the inhaler and disperse it into respirable particles. In addition to the inspiratory effort, some considerable “mental” effort is needed to use any inhalation treatment correctly. The non-adherence to the instructions for use, including incorrect technique, is about 50%, and it has not improved much with time (Gonda, 2019 and refs. therein). Additionally, in their ground-breaking publication that influencedmuch subsequent debate, Clark and Hollingworth (1993) pointed out that a fundamental attribute of each DPI was its flow resistance and that the inspiratory flow rate achieved through an inhaler depended on the patient’s inspiratory effort and the device resistance. They also highlighted the subtle opposing impact of an increased inspiratory flow rate by a patient: while it will likely lead to better powder dispersion into smaller physical (and aerodynamic) size, the increased velocity of the drug-carrying particles will enhance deposition higher up in the respiratory tract. That suggested that with the right design, the regional dose delivery from a DPI can be quite inspiratory flow independent if these opposing factors are exquisitely balanced. However, it does not appear that the development of the majority of currently approved DPIs that use mostly technologies from several decades ago made a deliberate attempt to achieve such “flow independence.”Does it matter? In a recent publication in this journal, Weers (2022) presents his perspective that the concerns of certain physicians treating COPD patients with inhaled bronchodilators may be unwarranted regarding the inability of some patients to exert adequate flow rates through their devices. He provides a summary of clinical data with this class of drugs, showing that the safety and efficacy of the approved bronchodilator DPIs are adequate for the majority of the patients, despite the fact that in the “standard” in vitro tests, the DPIs appear to show “flow-dependent” performance. Edited by: Philip Chi Lip Kwok, The University of Sydney, Australia