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Smokers and ex-smokers with chronic stable asthma did not respond to high dose oral corticosteroids
  1. Peter G Gibson, MD
  1. Hunter Medical Research Institute, John Hunter Hospital
 Newcastle, New South Wales, Australia

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 Q In patients with chronic stable asthma, is bronchodilator and symptomatic response to high dose oral corticosteroids affected by smoking status?

    Clinical impact ratings GP/FP/Primary care ★★★★★☆☆ IM/Ambulatory care ★★★★★☆☆ Respirology ★★★★★★☆


    Embedded ImageDesign:

    randomised, placebo controlled, crossover study.

    Embedded ImageAllocation:


    Embedded ImageBlinding:

    blinded {patients, clinicians, data collectors, outcome assessors, and data analysts}.*

    Embedded ImageFollow up period:

    2 weeks.

    Embedded ImageSetting:

    hospital clinics in Glasgow, UK

    Embedded ImagePatients:

    59 patients who were 18–55 years of age (mean age 42 y, 72% men; based on 50 patients), had chronic asthma, forced expiratory volume in 1 second (FEV1) of 50–85% predicted, and ⩾15% reversibility of FEV1 after nebulised albuterol (2.5 mg). Exclusion criteria: asthma exacerbation, use of oral corticosteroids, or respiratory tract infection within 4 weeks; recent peptic ulcer; glaucoma; pregnancy; or lactation. 17 patients were current smokers (smoked for ⩾10 pack-years), 11 were ex-smokers (smoked for ⩾10 pack-years and quit more than 1 y ago), and 31 had never smoked.

    Embedded ImageIntervention:

    oral prednisone, 40 mg, or identical placebo for 14 days. After a 2 week washout period, patients received the alternative treatment.

    Embedded ImageOutcomes:

    change in prealbuterol FEV1 after active treatment compared with placebo, morning peak expiratory flow (PEF), and a validated asthma control score (0  =  well controlled and 6  =  poorly controlled)

    Embedded ImagePatient follow up:



    Patients who had never smoked had improvement in prealbuterol FEV1 and asthma control scores with prednisone compared with placebo, whereas smokers and ex-smokers did not (table). Morning PEF improved in never-smokers and ex-smokers but not current smokers (table).

    Response to prednisolone v placebo according to smoking status in patients with stable chronic asthma*


    In patients with chronic stable asthma, a 2 week course of prednisolone improved FEV1 and asthma control scores in never-smokers, but not in smokers or ex-smokers.


    Oops! That’s how asthma researchers are responding to the results of the study by Chaudhuri et al. Several decades of randomised controlled trials about corticosteroid treatment in asthma have shown how exquisitely effective they are (NNTs of about 3 for preventing exacerbations),1 but only in non-smokers.

    Generalisability is “the degree to which the results of a study can be extrapolated to other circumstances, in particular to routine health care situations.”2 Seeing a patient who has respiratory symptoms and smokes is a routine (predictable!) healthcare situation. Imagine a situation where the most effective treatment for the most common chronic respiratory disease gets it wrong on generalisability.

    What can we learn from this? We’ll still give steroids for asthma because the confidence intervals for the effect size are sufficiently wide to indicate that there are definite responders within the smoking population. We’ll be less enthusiastic about the response, however, and urgently ask clinical trialists to evaluate long acting β agonists and inhaled corticosteroids for efficacy in patients with asthma who smoke. The results also emphasise more than ever the need for practitioners to be expert in smoking cessation techniques.

    The underlying biological mechanisms of smoking related corticosteroid resistance in asthma will teach us a lot about asthma, and early data suggest a different inflammatory process resembling non-eosinophilic asthma.3 Some mischievous types will try to explain this away by invoking definitions of asthma and COPD. But that’s all smoke and mirrors.


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    • * See glossary.

    • Information provided by author.

    • For correspondence: Professor N C Thomson, Western Infirmary, Glasgow, UK.

    • Source of funding: National Asthma Campaign.