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Wednesday, August 20, 2014

Do B2 agonists increase mucociliary clearance?

Along with improving lung function, there is some evidence that beta adrenergic agonists (B2) might enhance secretion clearance.  This might provide another reason for physicians to order scheduled B2 agonist therapy.

There have been a variety of studies on the subject, and they were all summed up well by Dr. Ruben Restrepo in the September, 2007, issue of RCJournal, "Inhaled Adrenergics and Anticholinergics in Obstructive Lung Disease: Do They Enhance Mucociliary Clearance?"

How beta agonists stimulate mucus secretion is a complex process.  Restrepo explains it this way:  
The effects of the B2 adrenergics on the airway are mediated by stimulation of the B2 receptors, which increases cyclic adenosine monophosphate, which is a regulator of ciliary beat frequency in human airway epithelia.  Because of their effect on ciliary beat frequency, B2 adrenergics have been considered mucokinetic medications and cough clearance promoters.  B2 adrenergic agonists increase passive movement of watter across the airway surface, via active transport of ions across the airway epithelium.  They also stimulate secretion production, primarily from their action on mucus-secreting cells and submucosal glands.  These actions combined increase the amount of mucus in the airways.  
The following are the studies:
  1. Sabeter et al showed that when studied with ipatropium bromide and placebo, only albuterol (Ventolin) and Salmeterol (Serevent) enhanced mucociliary clearance in sheep up to 12 hours after the breathing treatment. Salmeterol had the longest acting effect.
  2. Jones and Reid albuterol increased the number of secretory cells in rats, particularly in the most peripheral airways. However, they concluded that larger than normal doses were required for "maximal short-term effects on mucociliary clearance, which increases the risk of increased viscious mucus secretion."
  3. Guleria et all found no difference in mucociliary clearance with either albuterol, ipatropium bromide, beclomethasone and placebo.
  4. Both albuterol and salmeterol produced only a "slight (less than 20%) increase increase in ciliary beat frequency above baseline."
  5. Laube et al showed that a single administration of albuterol significantly improved mucoliliary clearanc, compared with baseline values.
  6. Cleary et al found that inhaled levalbuterol does not increase mucociliary clearance or cough clearance, compared to albuterol or placebo.
  7. Wong et al found a 4-fold increase in ciliary beat frequency 30 minutes after administration with fenoterol.  It also showed increased  mucus clearance, more coughs, lower sputum viscosity, and more sputum production 24 hours after treatment.
  8. Studies show that salmeterol stimulates faster and stronger ciliary beat frequency than does albuterol.  
  9. Piatti et all studies salmeterol on COPD and pneumonia patients, and "confirmed the ability of salmeterol to enhance 'only to a modest degree' ciliary beat frequency in both normal and COPD nasal epithelium.  
  10. Mossberg et all confirmed the "minimal stimulation effect of B2 adrenergics in chronic bronchitis."
  11. Bennet et al "suggested that the observed enhanced clearance with salmeterol may be primarily from its effect on the mucociliary apparatus, as opposed to the cough mechanism. There were many studies done on salmeterol.
  12. Hasani et al found no significant enhancement of mucociliary clearance in patients with asthma following 2 weeks of salmeterol versus placebo, and concluded that salmeterol's mucociliary clearance benefit was a result of increased airway patency.
  13. Melloni and Germouty studied the effects of formoterol, and discovered an increase in mucociliary clearance.  There are only minimal studies done on fenoterol.
  14. Studies are inconclusive as to the mucoliliary clearance of B2 agonists in patients with cystic fibrosis.  Some showed that it had an effect, while others show no effect. 
  15. Studies showed that there was no increase in mucociliary clearance after inhalations of ipatropium bromide.
  16. Tiotropium may marginally enhance mucociliary clearance. 
  17. Norton J. et al (2013 study) suggests that clenbuterol modestly enhanced mucociliary clearance in horses.

1.  It appears that both albuterol (Ventolin) does have mucociliary clearance abilities, although for maximal effect more than 0.5cc must be given with each treatment.  

2.  Albuterol seems to have better mucociliary clearance abilities than levalbuterl (Xopenex).  Albuterol seems to be the prescription of choice for patients admitted to hospitals, and this may explain why physicians insist on ordering albuterol Q4 or QID for patients, even those who present with no dyspnea, presenting with chronic bronchitis, emphysema, asthma, cystic fibrosis, and pneumonia

3.  Formoterol (Symbicort) probably has mucociliary clearance properties, although there have only been a few studies as to this date. It can probably be prescribed for this purpose.

3.  Salmeterol (Serevent, Advair) has greater mucociliary clearance abilities than albuterol, and therefore should be the prescription of choice for mucociliary cearance.

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