Researchers Determine Repeatability Limits, Predictive Equation for COPD Inhalers

July 31, 2020

Using data from 2 phase 2 trials, researchers were able to determine the peak inspiratory flow (PIF) repeatability limit, and show that the 2 highest of 3 PIF values met the repeatedly limit.

In order to achieve optimal treatment delivery in chronic obstructive pulmonary disease (COPD), it’s important for patients to have the respiratory strength to overcome the internal resistance of their dry powder inhaler (DPI) so as to disaggregate the powdered drug into fine particles for lung deposition. To this end, peak inspiratory flow (PIF) has been touted as a measure of a patient’s ability to use DPIs.

Despite this importance, a gap in knowledge exists when it comes to having robust quality criteria for determining a repeatability limit for measuring PIF. In search of this, researchers were able to determine the PIF repeatability limit, as well as show that the 2 highest of 3 values of PIF met the repeatedly limit.

The findings were recently published in CHEST, and according to researchers, provide guidance for measuring PIF against the simulated resistance of DPIs in both clinical practice and research studies.

The analysis used data from a phase 3 study (study 0149) in which patients took 3 measures of PIF, including before and after using the inhaled study drug, within 1 session. From there, researchers determined the repeatability limit by using each unique combination of 2 assessments, which they defined as the absolute difference between 2 measurements under identical conditions.

The researchers also used study 0149, in addition to a second phase 3 trial (study 0128), to determine the relationship between PIF measured by the In-Check DIAL device at 2 resistances:

  • Diskus (PIFD) (resistance 2)
  • Handihaler (PIFHH) (resistance 5)

They found repeatability limits of PIF (10 L/min against the resistance of the Diskus and 5 L/min against the resistance of the HandiHaler) were achieved by the overwhelming majority of patients (95%).

Importantly, researchers also determined that a PIFD of 60 L/min is roughly equivalent to a PIFHH value of 40 L/min after controlling for covariates including sex, weight, body mass index, forced vital capacity, and percent predicted forced expiratory volume in the first second.

“Based on these data, we recommend that at least 3 measures of PIF be undertaken, using the In-Check DIAL device, until the two highest measurements meet the repeatability limits, which is similar to the recommendations for spirometry,” researchers said. They added, “Although we cannot comment on the total number of measurements that might be performed, our data demonstrate a tendency for the highest PIF value to be obtained in the first 2 efforts.”

Investigators saw in study 0128 the average values for PIF at 0 resistance and PIFHH were 84.6 L/min and 57.3 L/min, respectively. In study 0149, average values for PIFD and PIFHH were 42.4 L/min and 29.0 L/min, respectively. According to the researchers, the lower PIFHH in study 0149 is likely due to its inclusion of patients with suboptimal PIF, defined as <60 L/min set to Diskus resistance.

Looking at the average difference between the 2 measurements from the same patients and averaged over all patients, researchers found “the mean difference between measurement attempts for PIFD and PIFHH was small, <5 L/min and <3 L/min, respectively.”

Barnes CN, Mahler DA, Ohar JA, Lombardi DA, Crater GD. Peak inspiratory flows: defining repeatability limits and a predictive equation for different inhalers. CHEST. Published online April 25, 2020. doi: 10.1016/j.chest.2020.03.072