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Brittle Asthma Thorax: First Published As 10.1136/Thx.53.4.315 on 1 April 1998

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Brittle Asthma Thorax: First Published As 10.1136/Thx.53.4.315 on 1 April 1998 Thorax 1998;53:315–321 315 Brittle asthma Thorax: first published as 10.1136/thx.53.4.315 on 1 April 1998. Downloaded from Jon G Ayres, Jon F Miles, Peter J Barnes The term “brittle asthma” was first used in uliser, and maintenance or courses of oral 1977 to describe patients with asthma who corticosteroids.9 However, it became apparent maintained a wide variation in peak expiratory that this definition of asthma based on PEF flow (PEF) despite high doses of inhaled variability required scrutiny if it was to be used steroids.1 It was coined at a time when patterns as a tool for epidemiological studies into severe of PEF variability were beginning to be asthma. The definition itself lacked precision described with respect to clinical patterns of since the phrase “considerable medical disease, such as the morning dip in PEF12and therapy” did not specify precise doses of treat- the “double dip” pattern of morning and ment such as inhaled steroid dose or use of evening dips3 seen in patients with less well nebulised bronchodilators. In addition, there controlled asthma. The brittle asthmatic PEF was no clear idea of the duration of observation pattern of variability was identified as a necessary before the label “brittle asthma” separate group, being described as chaotic could be applied. Further doubts were cast on showing no such obvious repeating pattern. a predominantly PEF based definition of brittle The significance of the brittle pattern was not asthma when the reliability of PEF meter read- completely clear at that time, although the ings came under question. Recent evidence inference was that these patients had more indicates that several makes of hand held severe asthma that was, by definition, more dif- mechanical PEF meters show non-linear inac- ficult to control. Three papers published curacy in their readings such that they tend to shortly afterwards showed that this chaotic underestimate low and high PEF readings pattern of PEF could lead to death from an 4–6 whereas the mid range readings are acute severe attack and the authors raised the overestimated.10 11 As a result, a prospective possibility that these patients tended to be evaluation of more than 10 000 patient days of poorly compliant with treatment. Nevertheless, PEF data from patients with severe asthma was not all non-compliant patients showed this undertaken, correcting for PEF meter inaccu- chaotic pattern, so clearly other factors were racy. A specified dose of inhaled corticosteroid important. However, it is not clear how these therapy was used—namely, more than 1.5 mg patients would fit into a classification of severe per day beclomethasone or budesonide or asthma which would include all those patients http://thorax.bmj.com/ more than 0.75 mg inhaled fluticasone propi- at risk of death or repeated hospital admissions. Some physicians are unhappy with brittle onate daily—and a definite period (150 con- asthma being classified as a separate asthma secutive days) over which such variability occurred was employed to overcome the phenotype, regarding these patients as simply 12 the severe end of the spectrum. However, it is transient PEF variability seen after acute our belief that definition of diVering asthma exacerbations or allergen exposures. Although phenotypes is important, so what follows it is our impression that a period of three represents our view that brittle asthma should months may be an acceptable period over be considered as a specific asthma phenotype. which to assess variability in the clinical on September 25, 2021 by guest. Protected copyright. We suggest how further study of patients of this context, this tighter case definition is needed type may help in unravelling the pathogenesis for epidemiological work and was used in a and treatment of at risk asthma. series of studies which explored aetiological/ risk factors for brittle asthma. However, this definition does not take into Definitions account those patients who are subject to sud- After Turner-Warwick’s initial definition of den severe life threatening attacks often on a brittle asthma, the term began to become used background of apparently good asthma con- in diVerent ways by diVerent physicians and in trol. Premenstrual asthma may be one such the first British Thoracic Society Asthma example as some women develop a marked Guidelines7 the term was used solely to drop in PEF in the few days before describe those patients with sudden, severe, life menstruation.13 Sometimes these premenstrual Heartlands Research threatening attacks, usually out of the blue. exacerbations are so severe that they necessi- Institute, Birmingham However, studies of asthma deaths have tate ventilation. To allow for this the following Heartlands Hospital, consistently identified PEF variability as a risk classification of brittle asthma is suggested: Birmingham B9 5SS, factor for death.4–6 8 More recently a definition Type 1 brittle asthma: characterised by a UK of brittle asthma based on PEF variability, maintained wide PEF variability (>40% diur- J G Ayres J F Miles amount of treatment, and repeated attacks has nal variation for >50% of the time over a period been proposed.9 Brittle asthma was defined as a of at least 150 days) despite considerable National Heart and diurnal PEF variability (amplitude % maxi- medical therapy including a dose of inhaled Lung Institute, London mum) of >40% for more than 50% of the time steroids of at least 1500 µg of beclomethasone SW3 6LY, UK (for example, 16 days a month) despite (or equivalent) (fig 1, lower plot). P J Barnes maximal medical treatment—namely, high Type 2 brittle asthma: characterised by sudden Correspondence to: doses of inhaled corticosteroids with repeated acute attacks occurring in less than three hours Professor J G Ayres. doses of inhaled bronchodilator, often by neb- without an obvious trigger on a background of 316 Ayres, Miles, Barnes 600 asthma are admitted for acute severe asthma but at erratic and unpredictable intervals, Thorax: first published as 10.1136/thx.53.4.315 on 1 April 1998. Downloaded from 500 although in general their use of health care resources is less than that of the type 1 patients. 400 Both types of patient may require ventilation in acute attacks, although there is no information as to whether patients with either type 1 or type 300 2 brittle asthma are likely to need ventilation for shorter or longer periods than ventilated 200 patients who do not have brittle asthma. It has, however, been shown that patients ventilated Peak expiratory flow (l/s) 100 for acute severe asthma whose asthma attack came on suddenly (less than three hours) are 0 12 3 4 567 more likely to be men and to have severe acidosis due to extreme hypercarbia, but are Days more likely to be ventilated for a relatively short Figure 1 Peak flow chart in a patient with type 1 brittle asthma before (C) and after (x) period of time.16 These patients would appear treatment with continuous subcutaneous terbutaline. to be similar to the patient with type 2 brittle apparent normal airway function or well asthma. In the same study patients who were controlled asthma. ventilated after a period of unstable asthma These definitions may not include all were likely to be ventilated for longer periods, patients who suVer repeated severe attacks and less likely to be so acidotic, and much more who might be labelled as having brittle asthma, likely to be female, perhaps similar to the but when beginning to try to disentangle these patients with type 1 brittle asthma. Rapid onset severe patients an initial definition has to be attacks have also been shown to be associated attempted. Future work may show that these with a predominance of submucosal neu- definitions may not stand up to critical analysis trophils compared with those with slower onset and alternatives might be found. For instance, attacks where eosinophils predominate,17 al- attention could be given to assessment of 100 though this may reflect the kinetics of granulo- and 50 day periods of peak flow variability as cyte infiltration. It is of interest that the type 2 criteria for inclusion as a definition. However, attacks, being both rapid in onset and in recov- as they stand they do provide a basis for ery, are similar in that way to the attacks research in this area. suVered by the patients involved in the Barcelona soya bean induced asthma outbreaks18 which could lend support to the Epidemiology hypothesis that allergic triggers are important http://thorax.bmj.com/ Little is known about the incidence or in type 2 brittle asthma. prevalence of brittle asthma, partly because of the problems with definition discussed above. MORBIDITY There is no doubt that it is rare but it is not Type 1 brittle asthma is a cause of significant possible to estimate the prevalence from any of morbidity with frequent accident and emer- the studies of “near miss” asthma. The West gency attendances and is a condition for which Midlands Brittle Asthma Register has identi- large amounts of medication are prescribed. fied 76 patients with type 1 or 2 brittle asthma Patients with type 1 disease are very likely to be within an approximate asthma population of using maintenance oral steroids (40% in the on September 25, 2021 by guest. Protected copyright. 300 000. A conservative estimate of the Birmingham series) and to suVer the eVects of numbers not yet identified by the register such therapy—for example, osteoporosis and would be around 150, giving an overall preva- weight gain. They also suVer almost uniformly lence for brittle asthma of 0.05% of all from oesophageal reflux19 which may be due in asthmatic patients. The type 1 patient is more part to their treatment with high doses of bron- likely to be female (2.5F:1M), most being aged 14 chodilators and consequent oesophageal between 18 and 55 years, whereas in patients smooth muscle relaxation.
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