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• Early onset of effect of salmeterol and fluticasone propionate in COPD
  Ben Ponsioen
  Published on: 20 May 2005
• Inhaled steroid and acute bronchodilation
  David E Simcock
  Published on: 20 May 2005

• Published on: 20 May 2005

  Early onset of effect of salmeterol and fluticasone propionate in COPD

  • Ben Ponsioen, General Practitioner
  • Other Contributors:
    • Richard Dekhuijzen and Arthur Bohnen

  Dear Editor,

  Vestbo et al. did an interesting secondary analysis of the results of the Tristan study in outpatients aged 40-70 years, with COPD (FEV1= 25-70% predicted, and reversibity...

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  Dear Editor,

  Vestbo et al. did an interesting secondary analysis of the results of the Tristan study in outpatients aged 40-70 years, with COPD (FEV1= 25-70% predicted, and reversibity <_10 predicted="predicted" fev1.="fev1." treatment="treatment" with="with" salmeterol="salmeterol" fluticasone="fluticasone" _50="_50" _500mcg="_500mcg" bd="bd" was="was" within="within" two="two" weeks="weeks" superior="superior" and="and" alone="alone" to="to" placebo.1="placebo.1" furthermore="furthermore" a="a" beneficial="beneficial" effect="effect" breathlessness="breathlessness" scores="scores" pefr="pefr" fev1="fev1" of="of" did="did" predict="predict" the="the" outcome="outcome" continuous="continuous" for="for" _1="_1" year="year" in="in" most="most" patients.="patients." p="p"/>These findings have implications for primary care. We have the following questions that all regard the selection of patients in primary care that may benefit inhaler therapy for COPD.

  First, the lung function was measured as ‘clinic FEV1’. Was the flow- volume loop used? And furthermore was the ‘clinic’ measurement of FEV1 done with an instrument equipped with a turbine system with rotating vane, that is commonly used in primary care settings? Or, was a pneumotachometer used, which seems to be the gold standard in the lung function laboratory? Could a difference between ‘clinic FEV1’ and FEV1 measured in a lung function laboratory have biased the results of the study?

  Second, 746 out of the 1465 participants were current smokers. The efficacy of inhaled corticosteroids (ICS) is diminished in smokers with asthma.[2] An effect on symptoms of the lower airways of ICS for two weeks was missing in smoking non-asthmatic adults who presented persistent cough to the general practitioner.[3] This is in line with the finding of Cox et al. that for four weeks treatment with ICS did not affect cigarette smoke-induced inflammation in current smokers without airflow obstruction.[4] Therefore, reanalysis of the current data while comparing the short-term outcomes (within two weeks) in smokers vs. non-smokers could be of interest.

  Third, a further analysis by severity of COPD is needed. For it was suggested that treatment of patients with chronic bronchitis and almost normal lung function (mean FEV1 95% of the predicted value (SD18%)) with fluticasone 250 mcg b.i.d does have a short term but no long term effect.[5] Do patients with more severe COPD show a better short as well as a better long term response to treatment with inhalers , compared with patients with les severe COPD?

  Further controlled trials of treatment in less severe COPD-patients in primary care with ICS, long acting beta2 agonists, anticholinergic drugs, and their combinations, could be needed. Then, symptom scores should include not only the breathlessness scores that were used in the current analysis, but also cough scores. Cough is a prominent symptom in the early stages of COPD.

  Fourth, patients with early stages of COPD in primary care show intermittent or episodic symptoms: ‘exacerbations’. It is thought that salmeterol/fluticasone combination treatment in particular induces rapid improvement in lung function, enhances exercise tolerance and reduces the perceived severity of exacerbations.[6] However, combination therapy did not significantly improve exacerbation rate compared with salmeterol or fluticasone alone. Therefore, the therapeutic regimens to be studied should concentrate upon short term effects of treatments. Further, the predictive value of the short term treatment effects for long term outcomes has to be studied. The current analysis made a first move for that.

  Lastly, intermittent, symptomatic or ‘as needed’ inhaler treatments for COPD must to be compared with continuous long term treatments as studied by Vestbo et al. This approach is supported by the recent findings that the outcomes of as-needed treatment with ICS in adults with mild persistent asthma, in terms of morning PEFR or number of exacerbations, was not different from sustained treatment for one year.[7]

  Finally, we hypothesize that the potential of salmeterol/fluticasone in COPD is in the exacerbation of non-smokers. If so, the ‘as-needed’ use of combination inhaler therapy for COPD it may optimise the benefit/side effects and benefit/cost ratio’s.

  References

  1. Vestbo J, Pauwels R, Anderson JA, Jones P, Calverley P. Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease. Thorax. 2005;60:301-4.

  2. Piipari R, Jaakkola JJ, Jaakkola N, Jaakkola MS. Smoking and asthma in adults. Eur Respir J. 2004;24:734-9.

  3. Ponsioen BP, Hop WC, Vermue NA, Dekhuijzen PN, Bohnen AM. Efficacy of fluticasone on cough: a randomised controlled trial. Eur Respir J. 2005 ;25:147-52.

  4. Cox G, Whitehead L, Dolovich M, Jordana M, Gauldie J, Newhouse MT. A randomized controlled trial on the effect of inhaled corticosteroids on airways inflammation in adult cigarette smokers. Chest. 1999;115:1271-7.

  5. van Grunsven P, Schermer T, Akkermans R, Albers M, van den Boom G, van Schayck O, van Herwaarden C, van Weel C. Short- and long-term efficacy of fluticasone propionate in subjects with early signs and symptoms of chronic obstructive pulmonary disease. Results of the DIMCA study. Respir Med. 2003;97:1303-12.

  6. Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulsvik A, Anderson J, Maden C; TRial of Inhaled Steroids and long-acting beta2 agonists study group. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2003;361:449-56.

  7. Boushey HA, Sorkness CA, King TS, Sullivan SD et al. Daily versus as- needed corticosteroids for mild persistent asthma. N Engl J Med. 2005;352:1519-28.

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  Conflict of Interest:
  None declared.

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• Published on: 20 May 2005

  Inhaled steroid and acute bronchodilation

  • David E Simcock, SpR and Clinical Research Fellow

  Dear Editor,

  Vestibo et al. report their surprise at the rapid effect of inhaled fluticasone propionate (FP) on symptoms of dyspnoea and PEFR improvements in COPD subjects.[1] A feasible explanation for their observation is suggested by considering the effects of FP on airway vascular biology in asthmatic and healthy individuals. The impressive work by Wanner et al. demonstrated that FP causes acute vasoconstrict...

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  Dear Editor,

  Vestibo et al. report their surprise at the rapid effect of inhaled fluticasone propionate (FP) on symptoms of dyspnoea and PEFR improvements in COPD subjects.[1] A feasible explanation for their observation is suggested by considering the effects of FP on airway vascular biology in asthmatic and healthy individuals. The impressive work by Wanner et al. demonstrated that FP causes acute vasoconstriction (maximal at 30 minutes) in the bronchial mucosa, as measured by the validated dimethyl ether uptake technique.[2] The mechanism is believed to be glucocorticoid- mediated enhancement of airway adrenergic and noradrenergic neurotransmission.[3] This acute vasoconstrictor response results in mucosal decongestion and reduced clearance of beta agonist from the airway. Both of these effects serve to reduce airflow obstruction as measured by patient symptoms and PEFR. The findings of Vestibo and colleagues suggest inhaled corticosteroid produce a similar effect in the COPD airway that may be of immediate benefit to the patient.

  References

  1. Vestibo J, Pauwels R, Anderson JA, et al. Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease.Thorax 2005;60:301-304.

  2. Kumar SD, Brieva JL, Danta I, et al. Transient effect of inhaled fluticasone on airway mucosal blood flow in subjects with and without asthma. Am. J. Respir. Crit. Care Med. 2000;161:918-921.

  3. Chang PC, van der Krogt JA, and van Brummelen P. Demonstration of neuronal and extraneuronal uptake of circulating norepinephrine in the forearm. Hypertension 1987;9:647-653.

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  Conflict of Interest:
  None declared.

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