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Four reviews and still no answers: our clinical definitions are at fault
Acute bronchitis is one of the commonest medical
problems managed by health services, and one of the important clinical
questions is whether antibiotics do any good. Fittingly, for such a
common problem, there have been four systematic reviews comparing
antibiotics with placebo for treating bronchitis. All, however, have
reached clinically unhelpful conclusions, which simply exposes the
perennial problem for all systematic reviews that demonstrate no or
only marginal benefits from the intervention: is there a subgroup that might derive benefit? It also exposes the procrustean nature of our
definitions of acute bronchitis.*
Three of the reviews included meta-analyses1-3 and one
was a qualitative systematic review of the literature.4
They include almost all the same studies, We speculate that these findings conceal a small group of patients with
pneumonia who obtain a large benefit from antibiotics hidden within a
larger group of patients without serious bacterial infection The lower respiratory signs are central to our argument as it is
possible to confirm pneumonia in patients with clear chests but not
possible to exclude it in the presence of signs.6 Each of
the primary studies except that of Howie et al7 attempted to eliminate patients with pneumonia. However, the exclusion method varied considerably from study to study: severe dyspnoea and fine crackles, localised crackles or wheezes, clinical signs, the option of
a chest radiograph, or a compulsory chest radiograph.8 The range of lower respiratory tract signs ranges from zero9
to 55%.10
Five studies were more likely to eliminate pneumonia by chest
radiograph or exclusion with any lower respiratory signs yet only two
found statistically significant results for benefit from antibiotics.
One of these discounted the positive findings as being due to multiple
comparisons, with 10 statistically different findings, six in favour of
erythromicin and four in favour of placebo out of 140 statistical
comparisons.8 In the five remaining studies that we do not
think effectively excluded pneumonia there were 0-23 significant
findings. In one of the reviews (Cochrane review by
Smucny11) analysis by lower respiratory signs found a
statistically significant improvement with antibiotics (relative risk
0.48, 95% confidence interval 0.26 to 0.89)12-15 This
suggests that antibiotics are effective in patients with lower
respiratory signs and a clinical diagnosis of acute bronchitis.
This does not help us decide if there is really an entity that
can be called acute bacterial bronchitis because we do not know how
many of those patients had pneumonia. Only a chest radiograph would
help in that dilemma. If antibiotics, in a research setting, were
effective in patients with lower respiratory tract signs and who had a
cough and productive sputum and a clear chest radiograph then it would
be possible to postulate the existence of acute "bacterial"
bronchitis. If such an entity exists then prescribing antibiotics in
this situation would not be so highly criticised.16 If the
patients had pneumonia in the original studies one may ask why did they
not present clinically. There are many potential answers: the pneumonia
may have resolved spontaneously or the patients may have been given
antibiotics, either by study or non-study doctors, without this fact
being recorded in the study manuscript.
The short term solution is only to analyse studies by symptoms (cough
and productive or purulent sputum) in groups according to the presence
or absence of lower respiratory tract signs. It would be far better to
have a review that contained data from only a few studies but was
analysed in a way that clinicians could be reasonably sure that they
were not dealing with some cases of pneumonia.
What can the practising clinician do while awaiting such analysis? The
use of antibiotics may be justified in those with lower respiratory
tract signs *Proscrustes was a mythical Greek who adjusted the
size of his guests so that they would fit his iron bed. We suggest that "acute bronchitis" is a "one size fits all" diagnosis.
(b.arroll{at}auckland.ac.nz) Department of General Practice and Primary Health Care,
University of Auckland, Private Bag 92019, Auckland, New Zealand
although Fahey et
al2 called their review a systematic review of acute cough
in adults and included unpublished data from Stephenson. They all came
to similar ambiguous and clinically unhelpful conclusions, the most
negative being, "the current literature does not support antibiotic
treatment for acute bronchitis,"4 while the most
positive concluded, "antibiotics may be modestly effective for a
minority of patients with acute bronchitis."3
that is,
who have viral infection, bronchospasm, or minor bacterial infection.
The problem stems from the multiple definitions of acute bronchitis in
the primary studies, all of which have been treated as a single entity
for the purposes of review or meta-analysis. The primary trials accept
patients with acute cough and either purulent or productive sputum.
This is contrary to the accepted diagnostic classification criteria for acute bronchitis (which are consensus based not evidence based) in
which patients need to have an acute cough and scattered or generalised
abnormal chest signs: wheeze and coarse or moist sounds
that is, signs
of lower respiratory tract disease.5
confirmed by 256 patients in four
studies11
or in those who are aged 55 or older and either
"feel ill" or have a "frequent daytime cough"
confirmed by 27 patients in one study.12 For other patients there is more
evidence for benefit from bronchodilators than from antibiotics
shown
in 80 patients in two studies.
14 17
The abstracts of all the reviews are
available at
http://hiru.mcmaster.ca/cochrane/centres/Canadian/
Timothy Kenealy
| 1. | Bent B, Saint S, Vittinghoff E, Grady D. Antibiotics in acute bronchitis: a meta-analysis. Am J Med 1999; 107: 62-67[Medline]. |
| 2. |
Fahey T, Stocks N, Thomas T.
Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults.
BMJ
1998;
316:
906-910 |
| 3. | Smucny JJ, Becker LA, Glazier RH, McIsaac W. Are antibiotics effective treatment for acute bronchitis? J Fam Pract 1998; 47: 453-460[Medline]. |
| 4. | Orr PH, Scherer K, Macdonald A, Moffat ME. Randomized placebo-controlled trials of antibiotics for acute bronchitis. A critical review of the literature. J Fam Pract 1993; 36: 507-512[Medline]. |
| 5. | Classification Committee of the World Organisation of Family Doctors. ICPC-2 international classification of primary care. 2nd ed. Oxford: Oxford University Press, 1998. |
| 6. |
Metlay JP, Kapoor WN, Fine MJ.
Does this patient have community-acquired pneumonia? Diagnosing by history and physical examination.
JAMA
1997;
278:
1440-1445 |
| 7. | Howie JG, Clark GA. Double blind trial of early demethyltetracycline in minor respiratory tract illness in general practice. Lancet 1970; i: 1099-1102. |
| 8. | Brickfield FX, Carter WH, Johnson RE. Erythromycin in the treatment of acute bronchitis in a community practice. J Fam Pract 1986; 23: 119-122[Medline]. |
| 9. | Stott NC, West RR. Randomised controlled trial of antibiotics in patients with cough and purulent sputum. BMJ 1976; 2: 556-559. |
| 10. | King DE, Williams WC, Bishop L, Shechter A. Effectiveness of erythromycin in the treatment of acute bronchitis. J Fam Pract 1996; 42: 601-605[Medline]. |
| 11. | Smucny J, Fahey T, Becker L, Glazier R, McIsaac W. Antibiotics for acute bronchitis (Cochrane Review). Cochrane Database Syst Rev 2000;4:CD000245. |
| 12. | Verheij TJ, Hermans J, Mulder JD. Effects of doxycycline in patients with acute cough and purulent sputum; a double blind placebo controlled trial. Br J Gen Pract 1994; 44: 400-404[Medline]. |
| 13. | Dunlay J, Reinhardt R, Roi LR. A placebo controlled double blind trial of erythromicin in adults with acute bronchitis. J Fam Pract 1987; 25: 137-141[Medline]. |
| 14. | Hueston WJ. Albuterol delivered by metered dose inhaler to treat acute bronchitis. J Fam Pract 1994; 39: 437-440[Medline]. |
| 15. | Williamson HA. A randomised controlled trial of doxycycline in the treatment of acute bronchitis. J Fam Pract 1984; 19: 481-486[Medline]. |
| 16. | Gonzales R, Sande M. What will it take to stop physicians from prescribing antibiotics in acute bronchitis. Lancet 1995; 345: 665[CrossRef][Medline]. |
| 17. | Hueston WJ. A Comparison of albuterol and erythromicin for the treatment of acute bronchitis. J Fam Pract 1991; 33: 476-480[Medline]. |
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