Are [[beta].sub.2]-agonists effective treatment for acute bronchitis or acute cough in patients without underlying pulmonary disease? A systematic review - Original Research

Journal of Family Practice, Nov, 2001 by John J. Smucny, Cheryl A. Flynn, Lorne A. Becker, Richard H. Glazier

TABLE 1

CHARACTERISTICS OF STUDIES INCLUDED IN SYSTEMATIC REVIEW OF THE
EFFECTIVENESS OF [[beta].sub.2]-AGONISTS FOR ACUTE BRONCHITIS OR
ACUTE COUGH

Study                             Participants
                    Quality
                     Score      N       Age Range

CHILDREN

Bernard, 1999      3 (1 2 0)   59    1-10 (mean=3.3)
(USA) (19)

Korppi, 1991       3 (1 2 0)   49    1-10 (mean=3.8)
(Finland) (23)

ADULTS

Littenberg, 1996   4 (2 2 0)   142   Adults (mean=32)
(USA) (20)

Hueston, 1994      4 (1 2 1)   46    Adults (mean=35)
(USA) (21)

Melbye, 1991       4 (1 2 1)   80    Adults (mean=35)
(Norway) (22)

Tukiainen. 1986    2 (1 1 0)   74    Adults (mean=38)
(Finland) (24)

Hueston, 1991      4 (1 2 1)   42    Adults (mean=38)
(USA) (25)

Study                               Participants

                          Illness                    Illness
                     Inclusion Criteria        Exclusion Criteria

CHILDREN

Bernard, 1999         Cough 1-14 days        Respiratory rate >35 or
(USA) (19)                                  abnormal lung examination

Korppi, 1991       Respiratory infection      Bronchial obstruction
(Finland) (23)     associated with cough

ADULTS

Littenberg, 1996        Nonspecific             Consolidation on
(USA) (20)          bronchitis or acute          examination or
                     cough of <4 weeks'            radiograph
                          duration

Hueston, 1994         Productive cough      Clinical or radiographic
(USA) (21)               of <30 days'              evidence of
                          duration                  pneumonia

Melbye, 1991         Acute respiratory      No evidence of pneumonia,
(Norway) (22)      infection with >1 week      sinusitis (without
                   of cough (95%) and/or      wheezing or dyspnea),
                       dyspnea (71%)             or tonsillitis

Tukiainen. 1986      Acute respiratory             Not stated
(Finland) (24)      infection with cough
                   (mean duration=8 days)

Hueston, 1991         Productive cough        No clinical or radio-
(USA) (25)         of <30 days' duration       graphic evidence of
                                                   pneumonia

Study              Participants
                   Withdrawals          Interventions

CHILDREN

Bernard, 1999          13         Albuterol syrup vs placebo
(USA) (19)                             syrup for 7 days

Korppi, 1991            3        Albuterol   dextromethorphan
(Finland) (23)                        syrup vs dextrome-
                                        thorphan syrup
                                       alone for 3 days

ADULTS

Littenberg, 1996       38           0ral albuterol sulfate
(USA) (20)                          vs placebo for 7 days

Hueston, 1994           0        Albuterol inhaler vs placebo
(USA) (21)                           inhaler for 7 days;
                                   each group also received
                                       erythromycin or
                                       placebo capsules

Melbye, 1991           11            Fenoterol inhaler vs
(Norway) (22)                          placebo inhaler
                                          for 7 days

Tukiainen. 1986    Not stated          Oral albuterol  
(Finland) (24)                         dextromethorphan
                                          tablets vs
                                       dextromethorphan
                                   tablets alone for 4 days

Hueston, 1991           8            Albuterol syrup vs
(USA) (25)                       erythromycin ethylsuccinate
                                       syrup for 7 days

* Maximum validity score=5. Components (randomization [0-2],
blinding [0-2], and reporting of withdrawals [0-1]) are in
parentheses.
TABLE 2

OUTCOMES FROM INDIVIDUAL TRIALS COMPARING [[beta].sub.2]-AGONISTS
WITH CONTROL FOR PATIENTS WITH ACUTE BRONCHITIS OR ACUTE COUGH

OUTCOME                                        STUDY

                                  Children                 Adults

                          Bernard (19)   Korppi (23)   Littenberg (20)

Daily daytime cough
scores                         NS            NS              NS

Daily nighttime
cough scores                   --            --              NS

Daily general condition
or total symptom scores        --            NS              --

Number with cough at
end of trial                   NS            --              NS

Number with night cough
at end of trial                --            --              NS

Number with productive
cough at end of trial          --            --              --

Average duration of
cough                          NS            --              --

Days until overall
improvement                    --            --              --

Days until return
to work                        --            --              NS

Use of additional
cough medications              --            --              NS

Additional health
care visits                    --            --              NS

Adverse effects           More shaking       NS         More days of
                          in albuterol                 shakiness and
                             group                     nervousness in
                                                       albuterol group

OUTCOME                                  STUDY


                                         Adults

                          Hueston 1994 (21)    Melbye (22)

Daily daytime cough
scores                           --                NS

Daily nighttime
cough scores                     --                --

Daily general condition
or total symptom scores          --                NS

Number with cough at
end of trial                  Fewer in             NS
                              albuterol
                                group

Number with night cough
at end of trial                  NS                NS

Number with productive
cough at end of trial            NS             Fewer in
                                               fenoterol
                                                  group

Average duration of
cough                            --                --

Days until overall
improvement                      --                --

Days until return
to work                       Sooner in            --
                              albuterol
                                group

Use of additional
cough medications                NS                --

Additional health
care visits                      --                --

Adverse effects                  NS            More tremor
                                              and palpita-
                                              tions in fe-
                                              noterol group

OUTCOME                                  STUDY

                                         Adults

                           Tukiainen (24)     Hueston 1991 (25)

Daily daytime cough
scores                           NS                   --

Daily nighttime                                        --
cough scores              Less in albuterol
                                group

Daily general condition
or total symptom scores          --                   --

Number with cough at
end of trial                     --               Fewer in
                                                  albuterol
                                                    group

Number with night cough
at end of trial                  --                   NS

Number with productive
cough at end of trial            --                Fewer in
                                                  albuterol
                                                    group

Average duration of
cough                            --                   NS

Days until overall
improvement                      --                   NS

Days until return
to work                          --                   NS

Use of additional
cough medications                --                   NS

Additional health
care visits                      --                   --

Adverse effects                  --            More nervousness
                                               or tremulousness
                                                in albuterol
                                               group; more gas-
                                              trointestinal side
                                               effects in ery-
                                               thromycin group

NOTE: All differences noted were statistically significant.
A blank cell indicates that the study did not report this outcome.
NS denotes no significant difference between the [[beta].sub.2]
-agonist group and the control group.
TABLE 3

STANDARDIZED MEAN DIFFERENCES (SMD) FOR DALLY COUGH SYMPTOM SCORES FOR
TRIALS IN CHILDREN AND ADULTS COMPARING [[beta].sub.2]-AGONISTS WITH
PLACEBO FOR ACUTE COUGH AND BRONCHITIS

Treatment Day         Number of   Number of   SMD in Cough Scores (*)
                       Studies    Patients        (95% Confidence
                                                      Interval)

STUDIES IN CHILDREN
Day 1                     2           96         0.35.(-0.05 to 0.76)
Day 2                     2           96         0.19 (-0.21 to 0.59)
Day 3                     2           95         0.36 (-0.05 to 0.77)

STUDIES IN ADULTS
Day 1                     3          250        -0.05 (-0.30 to 0.20)
Day 2                     3          251        -0.10 (-0.35 to 0.15)
Day 3                     3          251        -0.17 (-0.42 to 0.08)
Day 4                     3          251        -0.14 (-0.38 to 0.11)

* Standardized mean difference is the difference between the
mean score in the [[beta].sub.2]-agonist groups and the mean
score in the placebo groups divided by the within-group standard
deviations. A negative number indicates a lower (ie, better)
symptom score. A SMD of 0.2 is considered small, 0.5 moderate,
and 0.8 or greater large. (29)
TABLE 4

SUMMARY DICHOTOMOUS OUTCOMES FROM META-ANALYSIS OF PLACEBO-CONTROLLED
TRIALS IN ADULTS OF THE EFFECTIVENESS OF [[beta].sub.2]-AGONISTS FOR
ACUTE BRONCHITIS

                           Number of   Number of
Outcome                     Studies    Patients

Cough after 7 days             3          220
Night cough after 7 days       3          210
Productive cough after
 7 days                        2          119
Not working after 4 days       2          149

                           Patients with Outcome (%)

                           [[beta].sub.2]   Placebo
Outcome                    -Agonist Group    Group

Cough after 7 days               64           71
Night cough after 7 days         24           29
Productive cough after
 7 days                          38           52
Not working after 4 days         29           31

                                                 Absolute Risk
                            Relative Risk          Reduction
Outcome                        (96% CI)             (95% CI)

Cough after 7 days         0.86 (0.63-1.18)   0.10 (-0.11 to 0.31)
Night cough after 7 days   0.84 (0.54-1.33)   0.04 (-0.07 to 0.16)
Productive cough after
 7 days                    0.76 (0.32-1.84)   0.11 (-0.25 to 0.48)
Not working after 4 days   0.82 (0.28-2.34)   0.07 (-0.25 to 0.41)

CI denotes confidence interval.