Rethink use of dual bronchodilators in smokers without COPD

Dual bronchodilator therapy does not improve respiratory symptoms in current and former smokers with respiratory symptoms but preserved lung function, a study has shown.

The findings, from the Redefining Therapy in Early COPD (RETHINC) trial, debunk the common practice of prescribing bronchodilators to people with a history of smoking who do not meet the GOLD criteria for a diagnosis of COPD.

The RETHINC trial, presented at ERS International Congress and published in the NEJM, compared twice daily indacaterol/glycopyrrolate versus placebo for 12 weeks in 535 people with a smoking history of at least 10 pack-years.

The participants had a COPD Assessment Test score of at least 10 despite preserved lung function on spirometry.

The US study found no observable treatment effect.

The primary outcome, an improvement by more than 4 points in the St. George’s Respiratory Questionnaire (SGRQ) score after 12 weeks, was achieved by 56.4% of the treatment group and 59.0% of the control group (p=0.65).

Lead author Professor Meilan Han said in an ERS statement that clinicians have used inhalers for patients with respiratory symptoms and a smoking history either because they assume the patient has COPD or that the smoking-related symptoms could be helped by inhalers.

“We’ve assumed these medications worked in patients who don’t meet lung function criteria for COPD, but we never checked,” Dr Han said. “We now know these existing medications don’t work for these patients.”

Instead, smoking cessation therapy remains the primary management strategy for the current smokers.

Professor Han, Chief of Pulmonary and Critical Care at the University of Michigan, said the study also highlights the need for new treatments for these patients with respiratory symptoms.

“The next question is, can we develop more targeted therapies for these patients who are on the milder end of the spectrum?”

An editorial in the NEJM said there was growing interest in identifying young or middle-aged tobacco-exposed people with preserved lung function on spirometry who will ultimately develop COPD.

“…these persons could then receive therapeutic interventions during the earliest stages of disease, with the goal of halting disease progression and reducing future morbidity and mortality.”

It said spirometry cannot be used to identify the people at high risk for progression to COPD because the test was not sensitive enough in detecting small-airway disease.

“Forced oscillometry, the lung-clearance index (also known as the multiple-breath washout test), and imaging-based methods such as parametric response mapping with the use of computed tomography and functional and microstructural magnetic resonance imaging show promise for the detection of small-airway disease before the onset of airflow limitation on spirometry,” it said.

The editorial also said that patients in this group mostly had symptoms of cough and sputum production rather than breathlessness.

“Although bronchodilators are effective in ameliorating breathlessness and improving exercise tolerance, they are generally ineffective for cough.”

“Existing drugs for the treatment of COPD, such as inhaled glucocorticoids or phosphodiesterase-4 inhibitors, or new therapeutics such as P2X3 receptor antagonists may be more effective for the treatment of cough and sputum production related to smoking and could be considered for future evaluations in this patient population.”

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