Table 2 Summary of clinical study on bromhexine

Gieseking 1968 [9]

Observational

Biopsy from 9 adult patients with cavitated tubercolosis or carcinoma

4 mg 3 times/24 h

Increased secretion activity in the seromucus glands of the bronchial mucosa

-

Lorenz 1974 [13]

Observational

36 pregnant women

1 mg/kg/24 h

Increase > 50% in total phospholipid concentration in fetal surfactant

-

Crimi 1986 [15]

Observational

13 adult patients with chronic bronchitis

48 mg/24 h

Increase concentration of total phospholipids in bronchoalveolar fluid

-

Flavell Matts 1973 [18]

Observational

53 adult patients with asthmatic bronchitis and acute or chronic bronchitis

8-32 mg/3 times/24 h

Reduced mucopolysaccharide fiber systems in sputum

-

Bürgi 1974 [19]

Single-blind crossover

22 adult patients with chronic bronchitis

8 mg/3 times/24 h

Reduction in sputum glycoprotein fiber content and decreased viscosity

-

Shimura 1983 [20]

Observational

40 adults with chronic pulmonary diseases (excluding asthma)

24 mg/24 h

BHC does not influence the molecular structure of the mucus

-

Langlands 1970 [21]

Double blind randomized controlled trial

27 adult patients with exacerbations of chronic bronchitis

8 mg/3 times/24 h

No significant difference in respiratory function or mucus properties

Nausea (n = 1)

Stark 1973 [22]

Randomized controlled trial

42 adult patients with chronic bronchitis

48 mg/24 h

No significant difference in mucus characteristics

-

Götz 1970 [23]

Observational

20 adult patients with allergic asthma

16-24 mg/24 h

Increased gamma globulins in sputum

-

Kado 1976 [24]

Observational

13 adult patients with chronic bronchial infections

-

Increased concentrations of IgA and IgG in bronchial washings

-

Thomson 1974 [25]

Observational

9 adult subjects with chronic bronchitis

48 mg/24 h

Increased mucociliary clearence

-

Pavia 1979 [26]

Observational

43 adult patients with chronic bronchitis

-

Increased mucociliary clearence

-

Bergogne-Berezin 1979 [28]

Double blind placebo controlled stud

22 adult patients undergone bronchoscopy and received erythromycin

4-12 mg/24 h

Increased erythromycin concentration in bronchial fluid

-

Roa 1995 [29]

Double blind multicenter randomized controlled trial

392 adult patients hospitalized for uncomplicated bacterial lower respiratory tract infections receiving amoxicillin

32 mg/24 h

Better overall resolution of symptoms and cough; increased expectoration

Undefined (n = 6)

Lal 1975 [30]

Randomized crossover placebo-controlled trial

41 adult patients with stable chronic obstructive bronchitis receiving oxytetracycline

48 mg/24 h

Better subjective evaluation of sputum stickiness and physician assessment of outcome

Headache (n = 2) Stomacache (n = 2)

Nesswetha 1967 [32]

Double blind randomized controlled trial

242 adult patients with mixed respiratory conditions

15 mg/24 h

Reduced cough

No adverse events reported

Gent 1969 [33]

Cross sectional, double blind, placebo controlled study

48 adult patients with chronic bronchitis, asthma, emphysema or diffuse parenchymal lung disease

24 mg/24 h

Overall clinical and functional improvement

Diarrhea (n = 1) Headache (n = 1)

Hamilton 1970 [34]

Double blind randomized controlled trial

22 adult patients recovering from an exacerbation of chronic obstructive bronchitis

48 mg/24 h

increased sputum production and reduced sputum viscosity

No adverse events reported

Christensen 1970 [35]

Double blind randomized controlled trial

61 adult patients with chronic bronchitis

24 mg/24 h

Better overall clinical improvement and increased FEV1

-

Condie 1971 [36]

Single blind randomized controlled trial

31 adult patients with chronic bronchitis

24 mg/24 h

Reduced symptoms, increased sputum volume and PEFR

Nausea and abdominal distension (n = 3)

Matts 1974 [37]

Double blind randomized controlled trial

102 hospitalized adult patients with lower respiratory tract infections treated with oxytetracycline

32 mg/24 h

Higher rate of favorable response to treatment, faster recovery and shorter hospitalization stay

Nausea and anorexia (n = 22)

Armstrong 1975 [38]

Randomized crossover placebo-controlled trial

12 adult patients with chronic bronchitis

72 mg/24 h

Increased expectoration, improved auscultatory findings and PEFR

Headache and nausea (n = 1) Dizziness (n = 1)

Valenti 1989 [39]

Double blind multicenter randomized controlled trial

237 adult patients with chronic obstructive lung disease

60 mg/24 h

decrease in cough, dyspnea and sputum volume; easier expectoration; improved auscultatory findings and improved FEV1 and PEFR; higher rates of treatment efficacy

Vomiting and gastralgia (n = 1)

Bienvenido 1990 [40]

Randomized controlled trial

28 adult patients with acute bronchitis or exacerbation of chronic bronchitis receiving amoxycillin

24 mg/24 h

Reduced symptom severity and higher bacterial elimination

-

Olivieri 1991 [41]

Double blind multicenter randomized controlled trial

88 adult patients with exacerbation of bronchiectasis

90 mg/24 h

Improved cough, auscultatory findings, expectoration difficulty and FEV1

-

Aylward 1973 [42]

Double blind multicenter randomized controlled trial

38 adult patients with chronic obstructive bronchitis

48 mg/24 h

Reduced sputum viscosity and increased expectoration volume

Gastrointestinal (n = 1)

Barth 2015 [43]

Randomized double blind controlled parallel trial

177 adult patients with cough due to uncomplicated upper respiratory tract infections

24 mg/24 h

Better cough relief

Mixed (pruritus, diarrhea, abdominal pain, skin rash) (n = 6)

Tarantino 1988 [44]

Double blind randomized controlled trial

30 children with acute sinus inflammation receiving amoxycillin

48 mg/24 h

Reduced nasal secretions, improvement in rhinitis; less school days lost

No adverse events reported

Molina 1970 [45]

Observational

48 infants with pharyngo-bronchitis, bronchopneumonia, bronchopneumonia with tubercolosis and asthmatic bronchitis

4-24 mg/24 h

Better overall clinical improvement

-

Fernandes 1973 [46]

Observational

30 children with clinical symptom of mucus retention (asthma, common cold and bronchiolitis)

0.5 mg/kg

Overall clinical improvement in patients with asthma and common cold

No adverse events reported

Brezina 1973 [47]

Observational

45 children with bronchitis

-

Overall clinical improvement

No adverse events reported

Okamoto 1981 [48]

Observational

37 children with bronchitis, common cold, asthmatic bronchitis, asthma and bronchiectasis

0.4-0.6 mg/kg

Overall clinical improvement

No adverse events reported

Koga 1981 [49]

Observational

32 children with upper respiratory tract inflammation, acute bronchitis, bronchopneumonia and asthma

0.4 mg/kg/3 times/24 h

Improved expectoration

No adverse events reported

Camurri 1990 [50]

Open randomized comparative study

32 children hospitalized for acute bronchitis

24 mg/24 h

Improved expectoration and clinical outcom

No adverse events reported

Azzolini 1984 [51]

Open randomized comparative study

40 children with hypersecretory bronchopulmonary diseases (acute, asthmatic or recurrent bronchitis)

6-12 mg/24 h

Improved general clinical conditions, dyspnea and sputum viscosity

Nausea and regurgitation (n = 2)

Diarrhea (n = 1)

Boner 1984 [52]

Observational

100 children with respiratory tract infections

0.6-0-8 mg/kg/24 h

Overall clinical improvement and better resolution in patients with acute episodes

Gastric intolerance (n = 3)