Non-steroidal anti-inflammatory therapy for asthma
Authors: Arthur Banner
Journal: The Lancet (1998)

Author's replySir—O M Kon and D S Robinson reference a meta-analysis on methotrexate treatment.1Marin MG Low-dose methotrexate spares steroid useage in steroid-dependent asthmatic patients: a meta-analysis..Chest. 1997; 112: 29-33Crossref PubMed Scopus (64) Google Scholar This study showed that methotrexate treatment resulted in modest steroid-sparing effects, similar to that observed with cyclosporin. However, Marin concluded that long-term studies of both steroid and methotrexate toxicities were necessary before methotrexate could be recommended for routine clinical use. I do not disagree with Kon and Robinson that these alternative anti-inflammatory agents could be considered in certain patients with severe steroid toxicity. In these instances, the risk-benefit ratio would need to be assessed for each individual: this is different from a general recommendation for their use in all patients with severe asthmaA B Kay and N C Barnes draw attention to their study showing the steroid-sparing effects of cyclosporin in steroid-dependent asthmatics.2Lock SH Kay AH Barnes NC Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma..Am J Respir Crit Care Med. 1996; 153: 509-514Crossref PubMed Scopus (198) Google Scholar The study referred to in the table was their earlier investigation showing improvement in lung function with cyclosporin.3Alexander AGN Barnes NC Kay AB Trial of cyclosporin A in corticosteroid-dependent chronic severe asthma..Lancet. 1992; 339: 324-328Summary PubMed Scopus (312) Google Scholar The aim of this table was to comment on steroid-sparing effects only, and this fact was signalled in the original title for the figure. Unfortunately, “steroid-sparing” was omitted from the title in the published versions.S H Lock and co-workers' study2Lock SH Kay AH Barnes NC Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma..Am J Respir Crit Care Med. 1996; 153: 509-514Crossref PubMed Scopus (198) Google Scholar shows variable steroid-sparing effects in people with chronic asthma. The difference between the mean daily use of prednisolone in the cyclosporin and placebo treated groups was modest (4·4 mg). Although greater reductions in steroid use were achieved during the later weeks of the study, it was not clear that these reductions could be maintained with continued use. Whether the reduction in steroid toxicity could justify the additional toxicity incurred with cyclosporin is conjectural. Although the renal impairment incurred with cyclosporin was said to be reversible, longer treatment with low-dose cyclosporin has resulted in permanent morphological renal damage.4Zachariae H Kragballe K Hansen HE et al.Renal biopsy findings in long term cyclosporin treatment of psoriasis..Br J Dermatol. 1997; 136: 531-535Crossref PubMed Scopus (108) Google Scholar Aside from issues of drug toxicity, the use of cyclosporin does not lend itself to routine management. Careful monitoring is essential and rigorous attempts at steroid reduction are necessary to achieve the steroid-sparing effects cited.R Madhok and colleagues' remarks about terminology in describing these agents is appreciated. I did originally refer to these agents as alternative anti-inflammatory drugs, but this was changed for the published version. Although the designation alternative anti-inflammatory agents is commonly used in pulmonary research and published work, its meaning is not obvious to a general audience. The terms disease-modifying and steroid-sparing agents seem more appropriate. Author's reply Sir—O M Kon and D S Robinson reference a meta-analysis on methotrexate treatment.1Marin MG Low-dose methotrexate spares steroid useage in steroid-dependent asthmatic patients: a meta-analysis..Chest. 1997; 112: 29-33Crossref PubMed Scopus (64) Google Scholar This study showed that methotrexate treatment resulted in modest steroid-sparing effects, similar to that observed with cyclosporin. However, Marin concluded that long-term studies of both steroid and methotrexate toxicities were necessary before methotrexate could be recommended for routine clinical use. I do not disagree with Kon and Robinson that these alternative anti-inflammatory agents could be considered in certain patients with severe steroid toxicity. In these instances, the risk-benefit ratio would need to be assessed for each individual: this is different from a general recommendation for their use in all patients with severe asthma A B Kay and N C Barnes draw attention to their study showing the steroid-sparing effects of cyclosporin in steroid-dependent asthmatics.2Lock SH Kay AH Barnes NC Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma..Am J Respir Crit Care Med. 1996; 153: 509-514Crossref PubMed Scopus (198) Google Scholar The study referred to in the table was their earlier investigation showing improvement in lung function with cyclosporin.3Alexander AGN Barnes NC Kay AB Trial of cyclosporin A in corticosteroid-dependent chronic severe asthma..Lancet. 1992; 339: 324-328Summary PubMed Scopus (312) Google Scholar The aim of this table was to comment on steroid-sparing effects only, and this fact was signalled in the original title for the figure. Unfortunately, “steroid-sparing” was omitted from the title in the published versions. S H Lock and co-workers' study2Lock SH Kay AH Barnes NC Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma..Am J Respir Crit Care Med. 1996; 153: 509-514Crossref PubMed Scopus (198) Google Scholar shows variable steroid-sparing effects in people with chronic asthma. The difference between the mean daily use of prednisolone in the cyclosporin and placebo treated groups was modest (4·4 mg). Although greater reductions in steroid use were achieved during the later weeks of the study, it was not clear that these reductions could be maintained with continued use. Whether the reduction in steroid toxicity could justify the additional toxicity incurred with cyclosporin is conjectural. Although the renal impairment incurred with cyclosporin was said to be reversible, longer treatment with low-dose cyclosporin has resulted in permanent morphological renal damage.4Zachariae H Kragballe K Hansen HE et al.Renal biopsy findings in long term cyclosporin treatment of psoriasis..Br J Dermatol. 1997; 136: 531-535Crossref PubMed Scopus (108) Google Scholar Aside from issues of drug toxicity, the use of cyclosporin does not lend itself to routine management. Careful monitoring is essential and rigorous attempts at steroid reduction are necessary to achieve the steroid-sparing effects cited. R Madhok and colleagues' remarks about terminology in describing these agents is appreciated. I did originally refer to these agents as alternative anti-inflammatory drugs, but this was changed for the published version. Although the designation alternative anti-inflammatory agents is commonly used in pulmonary research and published work, its meaning is not obvious to a general audience. The terms disease-modifying and steroid-sparing agents seem more appropriate. Non-steroidal anti-inflammatory therapy for asthmaIn his Jan 3 commentary,1 Arthur Banner does not comment on several placebo-controlled trials of efficacy and steroid-sparing effects of non-steroidal anti-inflammatory drugs for asthma. Full-Text PDF Non-steroidal anti-inflammatory therapy for asthmaArthur Banner1 incorrectly states in his commentary that “cyclosporin…had steroid-sparing effects in asthmatic patients in open studies but not in one placebo-controlled trial”. A double-blind, placebo-controlled study, published in 1996,2 showed that low-dose cyclosporin A therapy, as compared with placebo, not only allowed a substantial reduction in oral corticosteroid doses in patients with severe corticosteroid-dependent asthma but also improved lung function. Furthermore, an earlier double-blind, placebo-controlled, crossover trial in which cyclosporin A was added to current medication showed that the frequency of disease exacerbations requiring an increased prednisolone dose was reduced by 48% in patients on cyclosporin compared with those on placebo. Full-Text PDF Non-steroidal anti-inflammatory therapy for asthmaArthur Banner's1 description of gold, methotrexate, cyclosporin, and other similar compounds as non-steroidal anti-inflammatory drugs (NSAIDs) for treatment of asthma is potentially misleading. NSAIDs is a term widely used to denote agents that affect the cyclo-oxygenase pathway, resulting in inhibition of prostaglandin synthesis. This action is responsible for their therapeutic, analgesic, and anti-inflammatory effects. This group of compounds may occasionally induce, rather than relieve, asthma. Full-Text PDF