TABLE 1

Inflammatory outcomes in clinical trials of asthma therapeutics

DrugAsthmatic group testedInflammatory outcomeReference
Corticosteroids
 PrednisoneMild, atopic, nocturnal↓ Airway neutrophilia; ↓ alveolar macrophage LTB4[87]
 Prednisone/deflazacortMild, uncontrolled↓ BAL LTB4 and PGE2 production[86]
 PrednisoneAtopic↓ Ex vivo alveolar macrophage LTB4 production[88]
 BudesonideMild, atopic↑ Alveolar macrophage IL-10; ↓ alveolar macrophage MIP-1α, IFN-γ and GM-CSF[66]
 ICS or ICS+LABAMild-to-moderate↑ Sputum IDO activity correlating with ↑ macrophage IL-10 production[91]
 PrednisoneMild↓ Alveolar macrophage IL-1β production[53]
 BeclomethasoneUncontrolled↓ BAL eosinophil and mast cell count; ↓ alveolar macrophage ROS correlated with improved airway hyperreactivity[92]
Macrolides
 ClarithromycinSevere, refractory↓ Sputum IL-8 and neutrophilia[103]
 AzithromycinSevere, FENO normalNo alteration in FENO[104]
 ClarithromycinModerate↓ TNF-α and IL-12 in BAL and airway tissue[106]
 ClarithromycinMild-to-moderateNo alteration in FENO[107]
Statins
 SimvastatinMild-to-moderateNo effect on airway and blood eosinophilia[174]
 SimvastatinMild-to-moderate, eosinophilic↓ Sputum eosinophilia in subgroup of patients[175]
 AtorvastatinMild-to-moderate, atopic↓ Sputum macrophage numbers and LTB4 production[130]
 SimvastatinMild↑ Sputum macrophage IDO activity and sputum IL-10; ↓ sputum eosinophilia[129]
 AtorvastatinSmokersNo change in sputum cell counts or cytokine levels[176]
 AtorvastatinMild-to-moderate, smokers↓ Sputum cytokine levels[132]
Phosphodiesterase inhibitors
 TheophyllineAtopic with allergen challenge↓ Airway tissue eosinophils[177]
 TheophyllineMild↓ Airway eosinophilia[178]
 TheophyllineMild↓ Sputum macrophage LTB4 production and neutrophilia[139]
 TheophyllineSevereTheophylline withdrawal led to ↑ monocytes and lymphocytes in airways[179]
 TheophyllineMild↑ HDAC activity in bronchial biopsy[138]
 RoflumilastMild, atopic↓ Late asthmatic reaction linked to inflammation[149]
 RoflumilastMild, atopic↓ Allergen-induced sputum eosinophilia and neutrophilia[151]

LTB4: leukotriene B4; BAL: bronchoalveolar lavage; PGE2: prostaglandin E2; IL: interleukin; MIP: macrophage inflammatory protein; IFN: interferon; GM-CSF: granulocyte–macrophage colony-stimulating factor; ICS: inhaled corticosteroid; LABA: long-acting β-agonist; IDO: indoleamine 2,3-dioxygenase; ROS: reactive oxygen species; FENO: exhaled nitric oxide fraction; TNF: tumour necrosis factor; HDAC: histone deacetylase.