Table 2 Overview of antifungal clinical studies (Chronological order)

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]