Peak inspiratory flow rate (PIFR) is an important consideration in the selection of an inhalation device in the management of chronic obstructive pulmonary disease (COPD), said Nicola A. Hanania, MD, MS, Director of the Asthma Clinical Research Center, and Associate Professor of Medicine, Sec tion of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, at a symposium sponsored by Sunovion, Inc, held at Chest 2010.
Patients with low PIFR may obtain greater therapeutic benefit from nebulized therapy, because unlike dry powder inhalers, nebulizers have minimal resistance and PIFR requirements for effective use.
PIFR is defined as the maximum amount of air that can be inhaled over the course of 1 deep breath, and is measured in L/min. A low PIFR, which is more common in older patients and those with more severe COPD, may result in inadequate drug deposition in the lungs when using dry powder inhalers, thus compromising drug efficacy, Dr Hanania explained.
“Why should internal resistance and PIFR matter? For the drug to work, it has to be deposited where you want it,” Dr Hanania said.
A low PIFR—defined as <30 L/min —results in greater drug deposition in the mouth and throat than in the lungs. Lung function is another important measure of effective drug delivery, and low PIFR correlates with poorer lung function, he said.
Although metered-dose inhalers (MDIs) also have minimal resistance and PIFR requirements, MDIs require coordination between actuation of the device and the inhalation for effective drug delivery. Patients must inhale with a slow, deep breath and then hold their breath when using an MDI.
“When choosing a delivery system, you want something the patient can accept. You have to choose the right drug and the right delivery system,” Dr Hanania said.
Coordination between device actuation and inspiration is not necessary for a nebulizer, he said, “and a nebulizer is effective with regular tidal breathing; deep breaths are not required.”
As nebulizers have become more portable, they have become more popular with patients. Approximately 25% of patients with COPD use nebulized therapy to manage their disease, according to Dr Hanania.
In a survey of patients with COPD, the advantages of nebulizer therapy were considered to outweigh any potential disadvantages of nebulizer therapy. The advantages cited were: • An increased feeling of well-being • Better symptom control • Increased confidence • Greater independence.
The GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines recommend intermittent short-acting beta-agonist therapy for patients with mild COPD, stepping up to the addition of ≥1 long-acting betaagonists (LABAs) with moderate or worse disease. The addition of inhaled corticosteroids is recommended for severe or very severe disease.
The 2 LABAs currently available in the nebulized format are arformoterol tartrate (Brovana) and formoterol fumarate (Symbicort).
Formoterol is a racemic mixture of the (R,R)- and (S,S)-isomers. Arformoterol contains only the (R,R)-isomer and is 1000 times more potent at receptor sites than formoterol, Dr Hanania said.
Arformoterol is approved for the treatment of COPD, to be dosed every 12 hours. In 12-week comparisons with placebo in patients with COPD, the improvement in forced expiratory volume in 1 second (FEV1) from baseline was significantly greater with arformoterol (15 μg) compared with placebo at the end of the 12-hour dosing interval. The mean FEV1 improvement from baseline was also superior with arformoterol versus placebo over the 12-hour dosing interval.
Shortness of breath was also reduced with arformoterol, as measured by the transitional dyspnea index (TDI) score. The mean improvement in TDI was 2.0 units with arformoterol compared with 1.1 units for placebo, Dr Hanania said.
Use of arformoterol was also associated with a reduction in the use of short-acting bronchodilators, he said. Daily rescue albuterol was reduced by 37% from baseline in arformoteroltreated patients compared with a 2% reduction in placebo recipients, and daily use of supplemental ipratropium was also reduced by 37% with arformoterol and by 9% with placebo. The percentage of patients reporting ad verse events was similar between arformoterol and placebo.