Primary care

Blockers for glaucoma and excess risk of airways obstruction: population based cohort study

James F Kirwan, research fellow ^a, Julia A Nightingale, specialist registrar ^b, Catey Bunce, medical statistician ^c, Richard Wormald, senior lecturer ^c. 

^a Department of Epidemiology and International Eye Health, Institute of Ophthalmology, London EC1V 9EL, ^b Royal Brompton Hospital, London SW3 6LY, ^c Moorfields Eye Hospital, London EC1V 2PD

Correspondence to: J F Kirwan jfkirwan{at}ucl.ac.uk

Topical  blockers are the most commonly prescribed drugs in the United Kingdom for glaucoma.¹ They are known to exacerbate bronchospasm in asthma and chronic obstructive pulmonary disease.² This study examined whether topical  blockers are associated with excess respiratory disease in elderly patients not considered to be at excess risk.

	Participants, methods, and results

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We used the Mediplus database to identify patients with no previous diagnosis of airways obstruction. We defined exposed patients as patients who had used ophthalmic topical  blockers for the first time in the period 1993-7. Unexposed patients were randomly selected (loosely matched by age and sex to exposed patients). For validation we inspected a random sample of 40 full longitudinal records of exposed and unexposed patients.

We defined patients who had excess respiratory disease in two ways. Definition A patients were patients who in the 12 months after treatment with topical  blockers were given for the first time a drug used for the treatment of reversible airways obstruction (₂ agonists, inhaled corticosteroids, theophyllines, and inhaled anticholinergics). Definition B patients combined definition A patients with patients who in the 12 months after treatment with topical  blockers had a new Read code for asthma or chronic obstructive pulmonary disease entered on their record.

Exposed patients (n=2645) were slightly older than unexposed patients (n=9094) (68.6 versus 67.5 years). Exposed patients were less likely than unexposed patients to smoke and to use systemic  blockers and were slightly more likely to visit their general practitioner (median six versus five visits). In definition A patients we found an adjusted hazard ratio at 12 months after treatment with topical  blockers of 2.29 (95% confidence interval 1.71 to 3.07)equivalent to a number needed to harm of 55 patients (table).

Of the 3358 patients (including patients with previous airways obstruction) begun on a topical  blocker during the study period, 148 (4.4%) had used drugs for airways obstruction within the previous year. Airways obstruction had been identified as an active problem (definition B) within the previous year in 316 subjects (9.4%).

	Comment

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Topical  blockers for glaucoma or ocular hypertension may lead to new airways obstruction requiring treatment in a population not considered to be at excess risk. This finding raises an issue of public health importance because of the large number (approximately 500 000) of elderly patients in the United Kingdom who are treated for glaucoma and ocular hypertension. Topical  blockers have been shown to affect respiratory function in elderly patients with no previous history of airways obstruction, although a small, short term study disputed this. ^{3 4} Our data indicate an attributable risk of 1000 patients per year in the United Kingdom, one case every 11 years for a general practitioner. One would expect the effect of  blockade on airways function to be rapidand indeed the risk ceases to be significant after the first year of exposure. This risk is in patients without previous airways obstruction; patients with pre-existing airways obstruction may well be more sensitive to  blockers.

Our study depends on a diagnosis of airways obstruction having been made. Therefore, allowing for a certain rate of missed diagnosis or misdiagnosis, we may have underestimated the true risk. An inherent weakness of the study is that clinical data could not be thoroughly validated. It is unlikely that objective spirometric evidence was always obtained. But for prescribing information the database is reliable, and a systematic error is unlikely to account for our findings.

Ophthalmologists, general practitioners, physicians, and pharmacists need to be aware of the possibility of iatrogenic airways obstruction in patients taking topical  blockers for glaucoma. When eyesight cannot be threatened within their expected lifetime, many frail elderly patients may be better off left untreated than risk airways obstruction.⁵  blockers should be discontinued immediately when a patient develops airways obstruction and their ophthalmologist subsequently informed. A repeat prescription that includes topical  blockers and drugs for asthma should automatically sound an alarm.

	Acknowledgments

We thank Trish Greenhalgh and Azeem Majeed for their helpful advice.

Contributors: JFK and RW designed the study. JFK and CB performed the analysis, and JFK, CB, RW, and JAN interpreted the results. JFK, CB, and JAN wrote the paper. JFK is the guarantor of the study.

	Footnotes

Funding: This study was funded by a grant from the International Glaucoma Association. JFK is supported by the Wellcome Trust (grant number 056045).

Competing interests: RW has been paid expenses to speak at meetings sponsored by companies marketing drugs for glaucoma. CB has received contributions towards travel expenses for two conferences from Pharmacia and Upjohn Ltd.

	References

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1.	Bateman DN, Clark R, Azuara-Blanco A, Bain M, Forrest J. The impact of new drugs on management of glaucoma in Scotland: observational study. BMJ 2001; 323: 1401-1402[Free Full Text].
2.	Charan NB, Lakshminarayan S. Pulmonary effects of topical timolol. Arch Intern Med 1980; 140: 843-844[Abstract/Free Full Text].
3.	Diggory P, Cassels-Brown A, Vail A, Abbey LM, Hillman JS. Avoiding unsuspected respiratory side-effects of topical timolol with cardioselective or sympathomimetic agents. Lancet 1995; 345: 1604-1606[CrossRef][Web of Science][Medline].
4.	Stewart WC, Day DG, Holmes KT, Stewart JA. Effect of timolol 0.5% gel and solution on pulmonary function in older glaucoma patients. J Glaucoma 2001; 10: 227-232[Medline].
5.	Quigley HA, Tielsch JM, Katz J, Sommer A. Rate of progression in open-angle glaucoma estimated from cross- sectional prevalence of visual field damage. Am J Ophthalmol 1996; 122: 355-363[Web of Science][Medline].

(Accepted 8 May 2002)