You are on page 1of 2

Case Report

Glucocorticoid-resistant Bronchial Asthma


Maj KS Brar

MJAFI 2004; 60 : 186-187

Introduction patient started showing improvement and his oral


prednisolone was gradually tapered off. Presently patient is
G lucocorticoids have potent anti-inflammatory actions
and are most effective agents in the treatment of
bronchial asthma. However, a subset of asthmatic
off steroids. He is on aerocort inhaler, sustained-action
theophylline and methotrexate 10 mg weekly. For the first
time in past 2 years, the patient, during review after 20 weeks,
patients do not benefit from glucocorticoid therapy. was without any wheeze and denied any symptoms. Single
Management of these patients with glucocorticoid breath count was 14. Chest examination revealed occasional
resistant bronchial asthma presents unique challenges rhonchi in both lung fields. He is off steroids for past 1
because of lack of effective and well-tolerated month now. Patient is tolerating methotrexate therapy quite
alternatives to steroids. Treatment should employ non- well without any adverse effects and is on regular monthly
steroidal agents as required to control symptoms. Recent follow-up.
experience with other immunomodulatory agents such Discussion
as cyclosporin, methotrexate and intravenous
immunoglobulin has highlighted their potential as steroid- The term “steroid resistant (SR) asthma” refers to a
sparing agents. This paper presents one such difficult group of asthmatics that have persistent airway
case. Relevant literature is briefly reviewed. obstruction and immune activation despite treatment with
high doses of systemic glucocorticoids. To make the
Case Report diagnosis of SR asthma, the patient must fail to respond
A 45 year old male, known case of bronchial asthma for to a 7 to 14 day course of daily prednisolone as measured
past 10 years, on regular bronchodilator therapy since then, by less than a 15% improvement in morning
presented with complaint of increased difficulty in breathing prebronchodilator FEV1 following the glucocorticoid
for past 2 years. Patient had been put on systemic steroids, course [1]. There are at least two forms of SR asthma,
along with other inhaled and oral bronchodilators since then i.e. primary and acquired types. Type 1 SR asthma is
and was on maintenance dose of Tab prednisolone 10mg/
acquired and is associated with abnormally reduced
day for past 12 months without relief.
glucocorticoid receptor (GCR) ligand and DNA binding
Clinical evaluation revealed middle-aged male with truncal affinity. Type II SR asthma appears to be due to a
obesity, blood pressure-140/100mm Hg, pulse-92/min, regular;
constitutive defect and is associated with low numbers
respiratory rate-32/min with accessory muscles of respiration
active. Patient was unable to complete sentences and his
of GCRs [2].
single breath count was 06. Chest examination revealed Before the diagnosis of a glucocorticoid resistant
bilateral scattered rhonchi. His routine hematological and asthma is made, a number of other entities that may
biochemical parameters were within normal limits. confound patient response to steroids must be excluded:
Patient was initially managed with oxygen at 4L/min, Medication noncompliance
systemic corticosteroids (Inj hydrocortisone 200mg IV stat
Occult occupational asthma with ongoing antigenic
and 100 mg IV 6 hourly), frequent (4 hourly) salbutamol
nebulization, IV aminophylline infusion and ipratropium
exposure
bromide 0.5 mg 6 hourly nebulization. Later, patient was Aspirin and NSAID sensitivity and exposure
switched over to asthalin and beclate inhalers, oral sustained- ABPA
action theophylline and oral prednisolone. The patient failed
to respond to a 14 day course of daily prednisolone (1 mg/kg/
Unrecognized food allergy
day) as measured by less than a 15% improvement in morning Unsuspected gastroesophageal reflux
prebronchodilator FEV1 following the glucocorticoid course Irreversible airflow obstruction
and was diagnosed as a case of glucocorticoid-resistant
bronchial asthma. Patient was started on Tab methotrexate
Underlying systemic vasculitis
10 mg weekly. During follow-up, over the next 16 weeks, Paradoxical vocal cord motion

Graded Specialist (Medicine), Military Hospital, Alwar.


Resistant Bronchial Asthma 187

The management of the SR asthmatic is challenging, noncompliance issues addressed. Alternative asthma
and every attempt should be made to maximize therapies are often used; however, they also carry the
conventional therapy in these patients prior to embarking potential for adverse effects, and have not been
on alternative therapies as all of the alternative anti- thoroughly studied in this population of asthmatic patients.
inflammatory/immunomodulatory modalities are Over the years, number of systemic steroid-dependent
associated with significant toxicity or cost [3]. Second- asthma patients has come down significantly as more
generation inhaled glucocorticoid therapy, methotrexate, effective inhalational delivery methods (like dry powder
cyclosporine, IVIG, and leukotriene antagonists are inhalers) and effective inhaled steroids have been
potential alternative therapies. Some success has been introduced. Cytotoxic agents and immune-modulators
achieved with conventional immunosuppressants such do play a significant role in reducing the need for steroids
as methotrexate, gold, and cyclosporin A. Leukotriene and symptom relief. Methotrexate 10 mg weekly has a
receptor antagonists have proved a useful addition to modest steroid-sparing effect [6,7] and is usually well
asthma therapy and have been shown to have a modest tolerated in this subset of patients.
steroid-sparing effect. Several new therapeutic agents References
have been developed to target specific components of
1. Nimmagadda SR, Spahn JD, Leung DY, Szefler SJ. Steroid-
the inflammatory process in asthma. These include IgE resistant astshma : Evaluation and management. Ann Allergy
antibodies, cytokines, chemokines, and vascular adhesion Asthma Immunol 1996;77(5):345-55.
molecules [4]. Similarly, preliminary studies of selective 2. Leung DY, de Castro M, Szefler SJ, Chrousos GP. Mechanism
phosphodiesterase inhibitors in asthmatic individuals have of glucocorticoid-resistant bronchial asthma. Ann NY Acad
been encouraging. Other potential therapies include Sci 1998;840:735-46.
platelet-activating factor receptor antagonists, tryptase 3. Dykewisz MS. Newer and alternative non-steroidal treatment
inhibitors and prostaglandin E analogs [5]. The continued for asthmatic inflammation. Allergy Asthma Proc
development of such targeted treatments should ensure 2001;22(1):11-5.
a greater diversity of therapeutic options for the 4. Frew AJ, Plummeridge MJ. Alternative agents in asthma. J
management of glucocorticoid resistant asthma in the Allergy Clin Immunol 2001;108(1):3-10.
new millennium. 5. Legg J, Warner J. Asthma the changing face of drug therapy.
Indian J Pediatric 2000;67(2):147-53.
The patient with SR asthma presents several
6. Domingo Ribas C, Comet Monte R, Bosque Garcia M, Moron
challenges. These individuals often display many of the Besoli A, Monton Soler C. Efficacy of methotrexate in the
sequelae of long-term systemic glucorticoid use while treatment of corticosteroid dependent asthmatic patients. Rev
achieving little therapeutic benefit. Prior to making the Clin Esp 1999;199(3):142-6.
diagnosis of SR asthma, diseases that can contribute to 7. Kazimierezak A, Maziarka D, Skorupa W, Kus J. Use of
poor control of asthma must be ruled out, and methotrexate for treatment of corticosteroid-dependent asthma.
Pneumonol Alergol Pol 1997;65(3-4):225-30.

MJAFI, Vol. 60, No. 2, 2004