Mucus Too Sticky? NAC Injections May Help

BARCELONA -- Patients with heavy mucus secretions that they couldn't readily expectorate obtained some relief with IV N-acetylcysteine (NAC), a researcher said here.

After 7 days of treatment in a randomized trial conducted in China, mean sputum viscosity scores declined by 0.24 points more with NAC than placebo injections (P<0.001), and scores for expectoration difficulty also decreased more with NAC by 0.29 points (P=0.002), according to Alberto Papi, MD, of the University of Ferrara in Italy.

NAC also proved non-inferior to ambroxol, another drug used to treat patients with stubborn mucus secretions, in terms of these outcomes, he reported at the European Respiratory Society (ERS) annual meeting.

"Overall, the study provides new evidence to support the efficacy and safety of IV NAC as a mucolytic and expectorant treatment in clinical situations where the IV route is preferred," Papi stated.

NAC is one of a number of treatments used as a mucolytic therapy, but the supporting evidence for its efficacy and safety is sparse. Papi said only a handful of studies have examined IV NAC for this purpose, none with more than 65 participants.

For the current study, Papi and colleagues enrolled 333 patients admitted with abnormal mucus secretions and acute respiratory illnesses. The latter included chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis, bronchiectasis, and others.

Sputum viscosity and expectoration difficulty, the trial's two co-primary endpoints, were each scored on four-point categorical scales, in which 0 represented normal function and 3 reflected severe abnormality ("sticky" for sputum viscosity, and "marked difficulty" with expectoration). Patients were included if their sputum was rated as sticky or viscous (score 2). Mean scores at baseline were about 2.2 both for sputum viscosity and expectoration difficulty.

Participants were randomized 1:1:1 to NAC, ambroxol, or placebo. Each was given by IV injection twice daily for 7 days, at 600 mg for NAC and 30 mg for ambroxol. Mean patient age was 65 and about two-thirds were men. Roughly half were never-smokers; about 60% of those with a smoking history had quit.

There were no differences between groups in sputum volume or changes in color, Papi said.

Adverse events (AEs) related to treatment were equally common with NAC and ambroxol, and severe/serious AEs were rare. Papi said the types of AEs seen with NAC were the same as reported in other studies.

In an ERS discussion, Frits Franssen, MD, PhD, of Maastricht University in the Netherlands, commented that the trial raised a number of questions, especially about its design. For one, he wondered whether the 7-day course of treatment meant that hospitalization was extended for some patients, in that they may not otherwise have needed a full week in the hospital. Franssen also questioned the choice of IV injection over oral treatment, which is readily available.

Papi responded that the investigators believed IV treatment may be more feasible in seriously ill patients "who might have difficulty with oral drugs," and therefore decided to focus on that in the trial.

Franssen also asked whether other medications patients were taking prior to admission might have affected the results. Papi replied that most patients were also on antibiotics and a portion had used traditional Chinese medicines, but these were "balanced between the two groups" and so should not have biased the results.

Comment