October 27, 2009 — 根據一項於10月20日發表於內科學誌（Annals of Internal Medicine）的隨機分派安慰劑控制研究結果顯示，吸入型類固醇（ICS）治療，對於沒有使用過類固醇的中重度慢性肺阻塞疾病（COPD）病患可能是有幫助的。
Therese S. Lapperre醫師與其來自GLUCOLD（Groningen Leiden大學肺阻塞疾病皮質類固醇）研究團隊的同事們寫到，ICS與長效β2-致效劑（LABAs）被用於治療中度到重度COPD。我們假設（1）以ICS作為長期維持療法可以提供抑制COPD病患氣管發炎作用（主要預後）；（2）這樣的作用與臨床改善有關；（3）停用ICS治療會誘發發炎與臨床狀況惡化；以及（4）ICS治療加上LABA並不能提供進一步的抗發炎作用。
部分研究作者表示皆與Nycome、Chiesi、Boehringer Ingelheim、GlaxoSmithKline、AstraZeneca、Altana、Teva、Top Institute Pharma、Glaxo Wellcome、Novartis以及/或是Innovative Medicines Initiative有資金上的往來。
Inhaled Corticosteroids May Be Helpful in Steroid-Naive Patients With Moderate to Severe COPD
By Laurie Barclay, MD
Medscape Medical News
October 27, 2009 — Inhaled corticosteroid (ICS) therapy may be helpful in steroid-naive patients with moderate to severe chronic obstructive pulmonary disease (COPD), according to the results of a randomized, placebo-controlled trial reported in the October 20 issue of the Annals of Internal Medicine.
"...ICSs and long-acting β2-agonists (LABAs) are used to treat moderate to severe...COPD," write Therese S. Lapperre, MD, and colleagues from the GLUCOLD (Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease) Study Group. "We hypothesized that 1) long-term maintenance therapy with ICS provides anti-inflammatory effects (primary outcome) in the airways of patients with COPD; 2) such effects are associated with clinical improvements; 3) discontinuing ICS therapy induces a flare-up of inflammation and clinical deterioration; and 4) adding a LABA to ICS therapy provides no further anti-inflammatory effects."
At 2 university medical centers in the Netherlands, 114 steroid-naive patients with moderate to severe COPD who were current or former smokers were randomly selected by the minimization method to receive fluticasone propionate, 500 μg twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 μg twice daily, and salmeterol, 50 μg twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29).
The primary endpoint of the study was cell counts in bronchial biopsies and sputum. Secondary endpoints were methacholine responsiveness determined at baseline, 6, and 30 months; and clinical outcomes evaluated every 3 months. Of the 114 participants, 101 patients were more than 70% adherent to therapy.
Compared with placebo, fluticasone treatment was associated with lower counts of mucosal CD3+ cells (–55%; 95% confidence interval [CI], –74% to –22%; P = .004), CD4+ cells (–78%; 95% CI, –88% to –60%; P < .001), CD8+ cells (–57%; 95% CI, –77% to –18%; P = .010), and mast cells (–38%; 95% CI, –60% to –2%; P = .039). Hyperresponsiveness was also reduced with fluticasone vs placebo at 6 months (P = .036), and these effects were maintained after 30 months.
Treatment with fluticasone for 30 months was associated with lower mast cell count and increased eosinophil count and percentage of intact epithelium. These improvements were mirrored by reductions in sputum neutrophil, macrophage, and lymphocyte counts as well as in improvements in decline of forced expiratory volume in 1 second (FEV1), reduced dyspnea, improved quality of life, and clinical improvements.
Patients who discontinued fluticasone therapy at 6 months had worsened clinical outcome and increased CD3+ cell counts (120%; 95% CI, 24% to 289%; P = .007), mast cell counts (218%; 95% CI, 99% to 407%; P < .001), and plasma cell counts (118%; 95% CI, 9% to 336%; P = .028). The addition of salmeterol was associated with improvement in FEV1.
"ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD," the study authors write. "Adding LABAs does not enhance these effects."
Limitations of this study were that it was not designed to assess clinical outcomes and that 24% of patients did not have primary outcome data at 30 months, creating possible selection bias. In addition, only data from adherent patients were used, and sample size was too small to draw conclusions about adverse events associated with ICS use.
"Our findings indicate that a subphenotype of patients with COPD who are steroid-naive and have moderate airway obstruction and airway hyperresponsiveness are sensitive to long-term ICS therapy," the study authors conclude. "These prolonged effects on inflammation and lung function do not imply causality but suggest that disease modification can be achieved in particular phenotypes of patients with COPD."
Netherlands Organization for Scientific Research, Netherlands Asthma Foundation, GlaxoSmithKline of the Netherlands, University Medical Center Groningen, and Leiden University Medical Center supported this study.
Some of the study authors have disclosed various financial relationships with Nycomed, Chiesi, Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Altana, Teva, Top Institute Pharma, Glaxo Wellcome, Novartis, and/or Innovative Medicines Initiative.
