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Table 2 Overview of antifungal clinical studies (Chronological order)

From: The role of antifungals in the management of patients with severe asthma

Antifungal Dose Route target Fungi n Design Duration benefits/outcome Refs.
Ketoconazole 400 mg, qd oral ABPA, Aspergiloma S 10 DB 12 M Af-IgG, symptom score (↓) Shale [85]
Itraconazole 50–400 mg, qd oral Aspergillosis
Aspergilloma
S 137 Open 11-780D 5 ABPA patients: Symptom (4/5↓) Fungus (3/4↓)
cure/improved:60% in IA, 66% in chronic necrotising pulmonary aspergillosis
De Beule [86]
Inhaled Natamycin 5 mg, bid inhaled ABPA S 25 DB 50 W 17 patient (9 natamycin, 8 placebo) completed
No evidence that natamycin conferred benefit on ABPA
Currie [87]
Itraconazole 200 mg, bid oral ABPA (CF, asthma) S C 6 Open 1-6 M (3.9 M mean) Symptom, tIgE, steroid use (↓),Af-IgG ( →), sputum culture negative in 2/3 Denning [88]
Itraconazole 200 mg qd oral ABPA S 12 Open  ≥ 6 M 11/12 improvement, blood eosinophil, tIgE (↓), Af precipitins -ve (7/12) Germaud [89]
Fluconazole 100 mg qd oral Asthma with dermatophytosis C 11 DB 5 M + 36 M bronchial sensitivity to Trichophyton, oral steroid use and symptom (↓) PEF(↑) Ward [68]
Itraconazole 200 mg qd oral ABPA S 14 Open 12 M Lung function (↑), blood esopinophilia, tIgE and steroid use (↓), Af-IgE ( →), Salez [90]
Itraconazole 200 mg bid oral ABPA S 55 DB 16 W Overall improvement (19% Placebo, 46% ITC), %change on tIgE -60% ITC vs. -44% PLB Stevens [58]
Itraconazole 400 mg qd oral ABPA S 29 DB 16 W Sputum eosinophil, ECP and serum tIgE/Af-IgG against A. fumigatus (↓), Exacerbation requiring oral steroids (↓),%change on tIgE -20% ITC vs. + 1% PLB Wark [59]
Itraconazole
Fluconazole
200 mg qd
150 mg qd
oral ABPA S 44 RS 6 M ITC > FLU: Better control of asthma symptom, less requirement of reliever/steroid, lesser exacerbation, vs. non-treatment Rai [91]
Itraconazole 200 mg bid oral SAFS S 58 DB 32 W AQLQ, Rhinitis score, PFT, tIgE (improved vs. Placebo). 60% large improvement. %change on tIgE -27% ITC vs. + 12% PLB Denning [61]
Itraconazole 100-450 mg qd oral ABPA
SAFS
S 33 RS  > 6 M Lung function (↑), tIgE, Af-RAST, eosinophil, steroid use (↓) Pasqualotto [92]
Voriconazole
Posaconazole
300-600 mg qd
800 mg qd
oral ABPA, SAFS
(Iraconazole-failed)
S 25 Open  ≥ 6 M Clinical response VOR (70% in), POS (78%) after 3 M treatment
tIgE, RAST-Af (↓) after ≥ 9 M treatment
Chishimba [13]
Voriconazole
(EVITA3)
200 mg bid oral Af associated asthma S 56 DB 3 M no difference on severe exacerbation, QOL, lung function, t or Af-IgE/IgG, blood/sputum eosinophil vs. placebo Agbetile [62]
Amphotericin B 10 mg bid nebulised ABPA, SAFS
(Itraconazole/voriconazole failed)
S 21 Open 30D (median)
0–1825D
14% (3/21) Clinical benefit
33% (7/21), failed initial dose due to Bronchospasm
52% (11/21), discontinued within 12 M
Chishimba [11]
Amphotericin B 10 mg bid thrice a week nebulised ABPA S 21 DB 4 M Frequency of exacerbation (↓ vs. nebulized budesonide), 3 patients, bronchospasm after nebulization of AMB Ram [12]
Itraconazole 200 mg bid oral ABPA (acute stage) S 131 DB 4 M ITC was effective, but overall efficacy: ITC < prednisolone, side effects ITC < prednisolone
The time to the first exacerbation: ITC = prednisolone
%change on tIgE -66% ITC vs. 67% PDS
Agarwal [10]
Voriconazole 200 mg bid oral ABPA (acute stage) S 50 unblinded, randomised 4 M VRC: Exacerbation, IgE, SGRQ(↓), Lung function (↑)
But, VRC appears to be as effective as prednisolone
Agarwal [93]
Amphotericin B 10 mg bid nebulised Pulmonary Aspergillosis S 177 RS 4 M to 6Y Poorly tolerated (66% only) due to increased breathlessness
Some patients showed t/Af IgE, Af-IgG(↓)
Otu [60]
  1. ABPA, Allergic Bronchopulmonary Aspergillosis; Af, Aspergillus fumigatus; AMB, Amphotericin B; bid, bis in die (twice daily); C, colonised (culture; PCR or any format of fungal detection); D, day; DB, double blind; ITC, itraconazole; M, month; PDS, prednisolone; POS, posaconazole; PLB, placebo; qd, quaque die (once daily); RS, retrospective; S, sensitised (blood IgE or skin); SAFS, Severe Asthma with Fungal Sensitisation; tIgE, total IgE; VOR, voriconazole; W, week; Y, year