Objective       To investigate the role of the combination of i

nhaled corticosteroid/long-acting β

2

agonist (ICS/LABA) and long-acting anti-cholinergic drugs (LAMA) in regulation of peripheral blood lymphocytes from patients with moderate asthma.       Methods       A total of 84 moderate persistent asthma outpatients (with asthma over 1 year

40%≤FEV

1

%≤60%) in the department of respiratory diseases

West China Hospital during November 2010 to December 2011 were randomly and equally divided into ICS/LABA group and ICS/LABA+LAMA group. Pulmonary function

asthma control test (ACT) score and asthma quality of life questionnaire (AQLQ) score were measured before and after administration. Western blotting was used to analyze β

2

receptor

M

3

receptor and PLCβ

1

in peripheral blood lymphocytes.       Results       The FEV

1

value

ACT score

and AQLQ score of the 84 patients were significantly improved after 24 weeks’ administering in both groups. Meanwhile

ICS/LABA/LAMA group improved more significantly (P0.05 in all). β

2

AR decreasing trend in ICS/LABA group was not obvious

the protein expression of M

3

R and PLCβ

1

was increased

and in ICS/LABA/LAMA group

β

2

AR level was unchanged the M

3

R was significantly decreased

and PLCβ

1

was noticeably increased.       Conclusion       Long-term administration of β

2

agonists may lead to the increased airway hyper-responsiveness

reduce bronchial protection effect

increase risks for acute exacerbation

and higher incidence of mortality. This phenomenon may be related to the activation or up-regulation of M

3

R and its pathway and desensitization of β

2

receptors. Combining with LAMA

the sensitivity of β

2

agonists might restore the antagonizing M

3

R

which therefore offset the adverse reactions caused by the desensitization of β

2

receptor

as well as activation of M

3

R and its pathway.