Is the term brittle asthma obsolete? What is its clinical relevance in routine practice?

Ravindran Chetambath; Jis B John

doi:10.4103/jalh.jalh_28_22

REVIEW ARTICLE

Year : 2023 | Volume : 3 | Issue : 2 | Page : 47-50

Is the term brittle asthma obsolete? What is its clinical relevance in routine practice?

Ravindran Chetambath¹, Jis B John²
¹ Department of Pulmonary Medicine, Baby Memorial Hospital, Kozhikode, Kerala, India
² Physician Trainee, NHS Trust, United Kingdom

Date of Submission	04-Sep-2022
Date of Acceptance	23-Oct-2022
Date of Web Publication	02-May-2023

Correspondence Address:
Dr. Ravindran Chetambath
Department of Pulmonary Medicine, Baby Memorial Hospital, Navaneeth, Sarovaram Biopark Road, Kozhikode - 673 020, Kerala
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jalh.jalh_28_22

Abstract

Brittle asthma is a life-threatening phenotype of asthma and was considered relevant in clinical practice before the year 2000. After the introduction of GINA guidelines, this entity was not discussed much in literature and the phenotype was included in acute severe asthma. Even the GINA guideline-2022 update is silent about this phenotype. This article discusses brittle asthma phenotypes and examines the relevance of this entity in clinical practice.

Keywords: Asthma phenotypes, brittle pattern, peak expiratory flow variability, terbutaline

How to cite this article:
Chetambath R, John JB. Is the term brittle asthma obsolete? What is its clinical relevance in routine practice?. J Adv Lung Health 2023;3:47-50

How to cite this URL:
Chetambath R, John JB. Is the term brittle asthma obsolete? What is its clinical relevance in routine practice?. J Adv Lung Health [serial online] 2023 [cited 2023 May 28];3:47-50. Available from: https://www.jalh.org//text.asp?2023/3/2/47/375535

Introduction

The term “brittle asthma” was first used in 1977 to describe patients with asthma who maintained a wide variation in peak expiratory flow (PEF) despite high doses of inhaled steroids.^[1] Brittle asthma is identified by the chaotic pattern of PEF variability without any identifiable repeatability. The clinical relevance of this brittle pattern was not completely clear, although it refers to a more severe asthma that was difficult to control. The exact incidence of these phenotypes in adults is unknown, but it seems to carry an increased risk of death and considerable morbidity. Adults with brittle asthma are generally atopic, with a high degree of psychosocial morbidity. The brittle asthma phenotype is not classified as a separate asthma phenotype in the present literature. But before evaluation by a specialist, all of the patients categorized as having problematic severe asthma should be subcategorized into difficult-to-treat asthma and true severe therapy-resistant asthma. Few patients under the category of difficult-to-treat asthma fit into the definition of brittle asthma and identification of this phenotype becomes relevant in clinical practice.

Definition

The British Thoracic Society (BTS) Asthma Guidelines,^[2] used the term solely to describe those patients with sudden, severe, life-threatening attacks appearing suddenly in an otherwise stable state. Brittle asthma was defined as a diurnal PEF variability of >40% for more than 50% of the time despite maximal medical treatment.^[3]

Classification

Brittle asthma is classified into two types

Type 1 brittle asthma which is characterized by a maintained wide PEF variability (>40% diurnal variation for >50% of the time over a period of at least 150 days) despite considerable medical therapy including a dose of inhaled steroids of at least 1500 μg of beclomethasone (or equivalent). Type 1 brittle asthma has chaotic swings in lung function, with a very labile peak flow
Type 2 brittle asthma is characterized by sudden acute attacks occurring in <3 h without any obvious trigger on a background of apparent normal airway function or well-controlled asthma. Type 2 brittle asthma is correlated with a high hospital admission for an acute severe attack, and is associated with higher mortality. The patients are well-controlled for a longer period, but when they have an attack, it is very severe and may require ventilation.^[4],[5]

Prevalence

Brittle asthma is a rare condition and its exact prevalence is not defined. Considering all asthma-related deaths and near-miss clinical states, it is estimated to be 0.05% of all asthmatic patients. The type one patient is more likely to be female (Male:Female = 1:2.5), most being aged between 18 and 55 years,^[6] whereas in patients with type 2 brittle asthma, there appears to be no sex difference. Patients with wide variations in PEF have an increased risk of dying from acute asthma.^{[7],[8],[9],[10]}

Type 1 brittle asthma is a cause of significant morbidity with frequent worsening and emergency attendances, and is a condition for which large amounts of medication are prescribed. Patients with type 1 disease are very likely to be using maintenance oral steroids and may suffer from many adverse effects of such therapy. They also suffer almost uniformly from esophageal reflux^[11] which may be due in part to their treatment with high doses of bronchodilators and consequent esophageal smooth muscle relaxation.

Risk Factors

Atopy, psychosocial factors, and food allergy were considered to be important risk factors for type 1 brittle asthma.^[6] For patients with type 2 disease, there are no published data on risk factors.

Over 90% of patients with type 1 brittle asthma are atopic. Type 1 brittle asthma is associated with increased sensitization to common allergens. Some patients with type 2 brittle asthma may be triggered by exposure to aeroallergens such as fungal spores.

Two-thirds of patients with type 1 brittle asthma report allergy to at least one foodstuff, with 20% reporting allergic reactions to peanuts.^[12] Equivalent data for patients with type 2 disease are not yet available.

Type 1 brittle asthma showed an increase in psychosocial morbidity. Psychological risk factors are prominent in children and young adults who subsequently die of asthma. Similarly, in near-fatal asthma episodes in children, the children also showed significant denial, psychosocial pathology, and delay in seeking treatment. These patients demonstrated abnormal coping strategies for managing deteriorating asthma. They delay going for medical help, self-treating by increasing β-agonist use, and trying to avoid either starting or increasing oral steroids. It is also reported that they have difficulty in symptom perception with consequent delay in seeking medical aid.^[13]

Treatment

Patients with brittle asthma are extremely difficult to manage. The standard management guidelines such as the GINA Guidelines or BTS guidelines^[2] are inapplicable to these patients once they have become brittle. They are already on large doses of inhaled steroids and the only way to increase the dose when the condition worsens is to resort to oral steroids which many resist because of side effects. It is also noticed that many patients use very large doses of β2-agonists, taken either as a metered dose inhaler (often more than one canister per week) or through a nebulizer.

Noncompliance has been much studied in mild-to-moderate asthma and is recognized to result from interaction of many factors, particularly psychosocial factors.^[14] The same is true of patients with brittle asthma who often resort to unconventional strategies to avoid having to start or increase the dose of oral steroids. Large improvement or control is unlikely in one step and many patients have more expectations than what they really get. Small successes, if perceived as such by the patient, can improve them psychologically.

Allergen Avoidance

Control of allergen exposure may be of help to a large extent in these patients. The logistics of allergen control are great, not only in terms of practicality but also cost-effective. Many patients with type 1 brittle asthma have animals at home and removal of what is often their best companion will be met with resistance. Unpublished data from the Birmingham group show that patients with brittle asthma are exposed to higher levels of pet allergens than other asthmatics, but whether this will result in the removal of pets and important reductions in allergen exposure in this severe group remains in doubt.

Steroids

These patients by definition are using high doses of inhaled and/or oral steroids, and the possibility of steroid resistance in at least some of these patients has been raised. Whether alternative immune-modulatory treatments such as methotrexate or cyclosporin A will be effective is not yet certain.

Subcutaneous β2-Agonists

Patients with type 1 brittle asthma can be treated with a long-term continuous subcutaneous infusion of terbutaline (CSIT). The usual dose of terbutaline is 3–12 mg/day^[15],[16] and 50% of patients with type 1 brittle asthma showed considerable improvements in symptoms and variation in PEF.^[17] Chronic steroid-dependent asthmatics without a wide variability in PEF did not respond to terbutaline infusion.

There are problems with CSIT which includes the development of subcutaneous nodules or inflammatory lesions. These usually settle down once that area of skin is avoided, but often leave a fibrotic nodule. Muscle cramps are common and sometimes may be severe, with an increase in the plasma levels of creatinine phosphokinase.^[18] Occasionally, menorrhagia is seen,^[3] but this is not usually severe.

Long Acting Inhaled β2 Agonists

In view of the marked fluctuations in PEF, it is expected that long-acting inhaled β2 agonists would be effective in stabilizing the airways. However, salmeterol has proved to be ineffective in these patients. There is an anecdotal report of a patient showing symptomatic and lung function improvement with formoterol.^[19]

Adrenaline

Adrenaline may be useful as an emergency treatment, particularly for patients with type 2 brittle asthma with their unexpected and rapidly progressive attacks. It is not yet certain whether inhaled adrenaline may be more effective than a selective β2-agonist inhaler.

Novel Therapies

New therapeutic approaches are urgently needed in the management of brittle asthma. In type 1 brittle asthma an alternative to steroids appears to be indicated. The role of type IV phosphodiesterase inhibitors or cytokine inhibitors is not so far worked out. The sudden and reversible airway narrowing in brittle asthma may be due to noninflammatory mechanisms and treatments such as tachykinin antagonists or opioids may be useful in some cases.

Anti-leukotriene (leukotriene receptor antagonists or 5-lipoxygenase inhibitors) may have a place in the management of some patients with type 1 brittle asthma. Some patients with more severe asthma appear to respond to this group of drugs^[20] which would merit a trial in patients with brittle asthma.

Psychogenic mechanisms are clearly important in some patients with brittle asthma. Not much attention has been paid to the influence of psychological factors on airway responses and whether psychological treatment can modify the course of the disease. Attention to coping with deteriorating asthma may help to reduce the amount of treatment used and may have an impact on hospital admissions.

Summary

Brittle asthma is a rare form of severe asthma that the clinicians may recognize and treat effectively, because of high morbidity and mortality. The question remains as to whether they are truly separate groups with entirely different pathogenetic influences or whether they simply represent the severe end of the spectrum of acute severe asthma. A prospective evaluation of patients with severe asthma is the only way of substantiating the validity of these definitions which will then enable the investigation of possible mechanisms. However, these patients are rare and to study them as a group a national registry is needed to keep a record of all at-risk patients with severe asthma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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