As cough, cold has become refractory, safe medicines preventing infection, avoiding steroids for long term is necessary

1. Respiratory conditions:
Role of Acebrophylline plus N-Acetylcysteine
* This slidedeck is for information purpose only. This has been prepared from data available on published evidence

2. Overview
 Pathogenesis of Mucus hypersecretion
 Conditions affected by Mucus hypersecretion/impaired mucus
clearance
 Long term effect of mucus hypersecretion if left untreated
 Importance of treating mucus hypersecretion
 Acebrophylline + N-Acetylcysteine
 Clinical evidence
 Guidelines/Recommendation for management
 Summary

3. Mucus hypersecretion

4. Pathogenesis of Mucus hypersecretion
 Studies have shown that inflammation and oxidative stress are
involved in the pathogenesis of chronic airway inflammatory diseases
and closely correlate with clinical outcomes
 They trigger excessive mucus production and secretion by glands
and goblet cells.
Shen Y,et al. Int J Chron Obstruct Pulmon Dis. 2018;13:399-407

5. Changes in airway in mucus hypersecretion
Duncan F et al.Pediatric Pulmonology 36:178–188 (2003)

6. Conditions affected by mucus hypersecretion/impaired mucus clearance
Shen Y,et al. Int J Chron Obstruct Pulmon Dis. 2018;13:399-407
JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY Volume 23, Number 4, 2010.
• Bronchitis
• Rhinosinusitis
• Otitis media with effusion
• COPD,
• Asthma,
• Bronchiectasis,
• Cystic fibrosis
• Lung cancer

7. Long term effect of mucus hypersecretion if left untreated
 Airway mucus hypersecretion, via chronic cough and expectoration,
reduces airflow and exercise capacity and increases the risk of acute
exacerbation, mortality, and poor prognosis in COPD patients
 Airway mucus hypersecretion facilitates bacterial colonization of
airways, limits airflow, and compromises ventilation in asthma
 Linked with airway mucus hypersecretion, airway inflammation and
damage occur in bronchiectasis patients, seriously affecting patients’
quality of life
 Airway mucus hypersecretion in patients with pulmonary cystic fibrosis
is associated with persistent cough, expectoration, and dyspnea.
Shen Y,et al. Int J Chron Obstruct Pulmon Dis. 2018;13:399-407

8. Benefits of mucus clearance and regulation
Given the important clinical significance of airway mucus hypersecretion
in chronic airway inflammatory diseases, expectorant therapy is widely
used to
 relieve airway stenosis,
 avoid recurrent infection and exacerbation, and
 delay decline in lung function.
Shen Y,et al. Int J Chron Obstruct Pulmon Dis. 2018;13:399-407

9. Role of Acebrophylline and NAC

10. Acebrophylline
MCC-Mucociliary clearance

11. PDE enzyme inhibition and bronchodilation
cAMP 5’ AMP
3’, 5’ GMP 5’ GMP
PDE
PDE
bronchodilation
Effects of Acebrophylline
Anti-inflammatory1
Immunomodulator2
Bronchodilation
Increased respiratory drive3
1 Sullivan P. Lancet 1994 Jun 11; 343: 1006-8
2Ward AJ, McKenniff M, Evans JM, et al. Am Rev Respir Dis 1993; 147: 518-23
3Ashutosh K, et al. J Clin Pharmacol 1997; 37: 1100-7
blocked by acebrophylline

12. Lacks adenosine receptor blockade
Adapted from: Ferritti C, et al, Int J Tiss Reac; 14(1): 31-36, 1992
Lastly, unlike theophyline, acebrophylline did not
antagonize adenosine receptor thus having more
specific action on PDE III and IV.

13. Mechanism of N-Acetylcysteine
Brandán Pedre, Uladzimir Barayeu, Daria Ezeriņa, Tobias P. Dick, 2021:228,107916,ISSN 0163-7258, https://doi.org/10.1016/j.pharmthera.2021.107916.
Santus P et al.COPD, 00:1–13, 2014.ISSN: 1541-2555 print / 1541-2563 online
Reduces
inflammation
Protection
against
irreversible
oxidative
damage
Reduces
viscosity of
mucus
secretion
Increase of
oxidant
scavenging
capacity
CYTOPROTECTION

14. Combination of N-Acetylcysteine with Acebrophylline
N-Acetylcysteine
• Antioxidant
• Mucolytic
• Anti-inflammatory
Acebrophylline
• Bronchodilator
• Anti-inflammatory
• Mucolytic
• Cardio-safety
●Bronchodilator
• Additive
• Anti-inflammatory
• Mucolytic
• Antioxidant
• Cardio-safety

15. Role of NAC in mucus hypersecretion
Perception that inhibiting mucus hypersecretion should have clinical benefit in hypersecretory
conditions of the airways
https://www.tandfonline.com/doi/full/10.1080/07853890600585795

16. Overall role of Acebrophylline + NAC combination
No pre-clinical or clinical studies are available on the combination of Acebrophylline plus
NAC.

17. Clinical studies on Acebrophylline and NAC

18. 50 mg/d- age 1-3 years
100 mg/d-age 4-6 years
150 mg/d-age 7-9 years
200 mg/d-age 10-12 years
Orally twice daily for 7 days
18
Reduced cough and sputum production with Acebrophylline in bronchitis
N-4313 children
Inclusion criteria:
• Diagnosed with acute
bronchitis Endpoints:
Efficacy and tolerability
Goldgrub N et al. Advances in therapy,1992;9(2):107-115
• Following treatment with acebrophylline, bronchospastic symptom of sibilus (whistling noise while
breathing) and dyspnea improved in 91% of patients and cough and sputum production was significantly
reduced.
• Only mild side effects (nausea, vomiting) were observed.
Bronchitis

19. Significant decrease in the amount of sputum and viscosity with Acebrophylline
Study [ref.], year Study characteristics Results
Milvio et al,1985 Double-blinded study, 41 patients treated
for 20 days
Asthma like bronchitis
Significant decrease in the amount of sputum and
viscosity especially in the patients given acebrophylline
Asthma like bronchitis

20. Acebrophylline was more active than ambroxol, in relieving clinical signs
Catena et al,1992 Multicentre, randomized, parallel groups
trial, enrolled 122 patients with asthma-like
chronic bronchitis (Ambroxol vs
acebrophylline for 45 days)
Acebrophylline was more active than ambroxol, in
relieving clinical signs
Asthma like bronchitis

21. Role of N-Acetylcysteine in chronic bronchitis
 Oxidative stress may be one of the key pathological mechanisms leading to lung
damage and potentially relevant systemic complications in COPD(chronic bronchitis).
 NAC having antioxidant properties can be effective.
L. Davies, P. M. A. Calverley, The evidence for the use of oral mucolytic agents in chronic obstructive pulmonary disease (COPD), British Medical Bulletin, Volume 93, Issue 1, March
2010, Pages 217–227,

22. Role of N-Acetylcysteine in chronic bronchitis
Associated with clinical benefit
 Both in terms of an improvement in the symptoms and signs present in the
condition and
 Also in a reduction in the incidence of acute infectious exacerbations
Jackson IM et al. J Int Med Res (1984) 12, 198
N-acetylcysteine has been
shown in vitro to reduce
the viscosity of the sputum
obtained from patients with
chronic bronchitis
Cleavage of the disulphide
bonds in mucus
glycoprotein, a major
component of sputum
Chronic bronchitis

23. Significant improvement in cough severity and difficulty in expectoration in patients with
chronic bronchitis treated with NAC
Primary outcome:
• Improvement in symptoms
• Global assessment by participating physicians
• Safety
Jackson IM et al. J Int Med Res (1984) 12, 198
multicentre, double-blind, placebo controlled. between-patient study in general
practice
N=121
Inclusion criteria:
• patients of either sex
suffering from chronic
bronchitis
(N-
Acetylcysteine)
Placebo
Chronic bronchitis

24. Results: Significant improvement in cough severity and difficulty in
expectoration in patients with chronic bronchitis treated with N-acetylcysteine
 Difficulty in expectoration: The improvement in
the group receiving N-acetylcysteine was greater
than placebo group.
 Cough severity. The difference between the
mean scores for the two groups did approach
conventional levels of statistical significance (p =
0·082).
 No serious side-effects attributable to N-
acetylcysteine therapy occurred during the trial.
Jackson IM et al. J Int Med Res (1984) 12, 198
Significant improvement in cough severity and difficulty in expectoration in patients
with chronic bronchitis treated with N-acetylcysteine
Global assessment by participating physicians
showed a difference in outcome in favour of N-
Acetylcysteine which approaches conventional
levels of statistical significance (p = 0·063).
Chronic bronchitis

25. Rationale of N-Acetylcysteine in Rhinosinusitis
• N-acetylcysteine reduces mucus viscosity and promotes mucociliary clearance.
These characteristics address two big issues of rhinosinusitis:
• mucus presence and
• altered mucociliary transport.
Macchi A, Terranova P, Castelnuovo P. Recurrent acute rhinosinusitis: a single blind clinical study of N-
acetylcysteine vs ambroxol associated to corticosteroid therapy. Int J Immunopathol Pharmacol. 2012 Jan-

26. Rationale of N-Acetylcysteine in Rhinosinusitis
 The treatment of these diseases often requires the combination of medical and surgical
strategies.
 In particular, the aim is to treat the infection (with antibiotics), to reduce the mucosal
swelling (with corticosteroids) and to improve mucus drainage (with mucolytics or muco
regulators).
 In acute recurrent rhinosinusitis the primary aim is to reduce the number of exacerbations
and increase the time between episodes, allowing a good quality of life
 In many studies, the only substance that showed significant effect on mucus reduction was
N-Acetylcysteine(N-Acetylcysteine)
Macchi A, Terranova P, Castelnuovo P. Recurrent acute rhinosinusitis: a single blind clinical study of N-acetylcysteine vs ambroxol associated to corticosteroid therapy. Int J
Immunopathol Pharmacol. 2012 Jan-Mar;25(1):207-17.

27. Phase III clinical study, monocentric, randomized, parallel groups, single blind, experimental
treatment
Group A: 1 vial of Flunisolide 0.1%
2 mL solution and 1 vial of N-
acetylcysteine 300 mg/3mL
solution administered by nasal
douche atomizer BD
27
Symptomatic improvement by N-Acetylcysteine in rhinosinusitis
J. Evolution Med. Dent. Sci./eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 9/ Issue 04/ Jan. 27, 2020
Group B: 1 vial of Flunisolide 0.1%
2 mL solution and 1 vial of
Ambroxol 0.75% 2 mL solution
administered by nasal douche
atomizer BD
N=139, Duration-20 days
• Age ~18 years;
• Patients affected by
recurrent acute
rhinosinusitis with
the evidence of ≥4
rhinosinusitis
exacerbations during
one year.
• Bacterial etiology
was excluded.
Primary objective
• proportion of patients who experienced
a symptomatic improvement at the end
of the nasal douche treatment.
Secondary objectives
• Number of disease exacerbations,
treatment acceptability
Multiple recurrent episodes of acute bacterial rhinosinusitis (ABRS) (3–4 episodes per year) suggesting
chronic sinusitis
http://clinicalestablishments.gov.in/WriteReadData/4221.pdf
Rhinosinusiti
s

28. Symptomatic improvement by N-Acetylcysteine
• Proportion of patients who scored 0 ("absence") in pain rose from about 30% at baseline to 77.33% and
45.33% for N-acetylcysteine and ambroxol,
• In nasal obstruction, score 0 was recorded in a proportion of patients that rose from 17.33% at baseline
to 62.67% for N-acetylcysteine and from 10.67 % to 32% for ambroxol;
• In endonasal hyperaemia from 8.00% to 50.67% for N-acetylcysteine and from 10.67% to 22.67% for
ambroxol
• In nasal irritation from about 60% to 88% and 68% for N-acetylcysteine and ambroxol, respectively;
• In nasal dryness from 66.67% to 92% for N-acetylcysteine and from 62.67% to 72% for ambroxol;
• In anosmia from 65.33% to 80% for N-acetylcysteine and from 61.33% to 77.33% for ambroxol; finally
• In cough from 81.33% to 93.33% for N-acetylcysteine and from 80% to 89.33% for ambroxol.
The group treated with flunisolide + N-Acetylcysteine had a significantly (chi-square 0.0001) greater proportion of
patients showing symptomatic improvement compared to flunisolide + ambroxol.
Rhinosinusiti
s

29. Reduction in exacerbations with N-Acetylcysteine
Time to the first exacerbation
J. Evolution Med. Dent. Sci./eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 9/ Issue 04/ Jan. 27, 2020
• At 3-month and 6-month follow-up, the number of observed
exacerbations was significantly lower in the flunisolide + N-
acetylcysteine group compared to flunisolide ambroxol group.
• The number of subjects with at least one exacerbation was
significantly lower in the N-acetylcysteine group compared to
ambroxol, with a >50% reduction of exacerbations at each visit.
• Furthermore, the time between the end of the treatment and the
first exacerbation was significantly longer in the N-acetylcysteine
group compared to the ambroxol group,
Rhinosinusiti
s

30. Better Safety of N-Acetylcysteine
J. Evolution Med. Dent. Sci./eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 9/ Issue 04/ Jan. 27, 2020
• Proportion of patients who developed an adverse event was lower in the flunisolide + N-acetylcysteine
group compared to the flunisolide + ambroxol group (18.67% vs 52%, respectively).
• Patients' and investigator's judgements were very positive,
• Compliance was high,
• Number of adverse events was lower, and
• No serious adverse event occurred.
• Tolerability profile of the flunisolide +N-acetylcysteine treatment was therefore definitely good, and
better than that of the flunisolide+ambroxol.
Adding N-acetylcysteine to the standard treatment improves patients' conditions, with effects that last up
to six months after the end of the treatment.
Rhinosinusitis

31. N-acetylcysteine stimulates sinonasal cilia beat frequency in-vitro
Results: Maximal stimulatory effect on cilia function
was evident at 10 mg/ml N-Acetylcysteine
concentration. After wash up, cilia movement were
increased very dramatically. This increase of cilia beat
frequency was even higher after N-Acetylcysteine plus
IBMX and N-Acetylcysteine plus ATP washings.
ENT Updates 2015;5(3):87–92
ATP- adenosine triphosphate
IBMX-isobutyl-1-methylxanthine
Methods: Well-differentiated human
bronchial epithelial cultures grown at an
air liquid interface were treated on the
apical or basolateral surface with varying
concentrations of N-Acetylcysteine.
The effects of N-Acetylcysteine were
evaluated on cilia beat frequency.
After the effect of N-acetylcysteine on
beat rate was found, its efficiency was
investigated by ATP or IBMX to
understand its mechanism of action.
Apical application of N-Acetylcysteine prominently stimulates cilia beat frequency and after wash up, cilia
movement was increased very dramatically.
Sinonasal cilia beat frequency

32. Randomized, double-blind and placebo-controlled study
Healthy volunteers were
included.
• Exclusion criteria consisted
of
 any anatomical defects of
the upper respiratory
system,
 history of trauma, history of
chronic nasal and
respiratory diseases
(asthma, rhinitis, COPD,
nasal polyps),
 history of taking drugs that
influence mucociliary
clearance,.
Saccharin test
The Mucociliary Clearance
Time (MCT) was measured
by saccharine test;
measuring the time in
minutes required for the
subject to taste a saccharin
particle placed on the inferior
turbinate of the nasal.
Saccharin Test Time (STT)
before and taking the
placebo or N-Acetylcysteine
was noted.
Healthy individuals (N=100)
32
N-acetyl Cysteine exerts measurable effect on nasal mucociliary clearance
Results:
• The mean times of case group before and
after taking N-Acetylcysteine showed a
00:54’’ difference, with a positive fluxion
nearly three-fold compared to the control
group.
• There was also a significant difference
between STT before and after taking the N-
Acetylcysteine with 95% assurance
(p=0.021), confirming the positive impact of
N-Acetylcysteine on nasal mucociliary
clearance.
N-acetyl Cysteine exerts measurable effect on nasal mucociliary clearance in healthy volunteers and therefore is
beneficial in conditions associated with disruption of mucociliary clearance such as rhinitis and sinusitis diseases as
much as pulmonary diseases as an adjuvant.
Rhinitis, COPD, nasal polyps and asthma

33. Effect of N-acetylcysteine on the Incidence of Recurrence of Otitis media with
Effusion and Re-insertion of Ventilation Tubes
Primary outcome
• Episodes of otorrhea,
recurrence of OME
after VT extrusion
and re-insertion of
VTs
Ovesen T et al. Acta Otolaryngol 2000; Suppl 543: 79–81
Double-blind, placebo-controlled, randomized
trial
N=75 children
Inclusion
criteria:
undergoing their
first bilateral
insertion of
ventilation tubes
(VT) due to OME
Mucomyst
(N-
Acetylcysteine)
The contralateral ear underwent VT insertion exclusively.
Instillation of Mucomyst or placebo was repeated 3 and 7
days afterwards. The children were followed
regularily for 11–39 months.
Placebo
The results demonstrated that Mucomyst significantly reduced the recurrence of OME and re-
insertion of VTs (p<0.025) and significantly increased the time until VT extrusion (p<0.0167).
In addition, the number of episodes of ear problems and visits at the ENT clinic were reduced
significantly by N-Acetylcysteine (p<0.0383).
on one ear in relation to the
VT insertion.
Otitis media with Effusion

34. Significant improvements in cough intensity and frequency in patients treated
with Acebrophylline
Beulcke G. Acebrophylline and theophylline in the treatment of bronchial asthma. An open comparative, randomized study. Acta Therapeutica 1995;21(2):101e11.
Improvements in cough intensity and cough frequency in Acebrophylline at days 2 and 3 (P<0.05 for both) and
at days 4 to 10 (P<0.01 for all 7 days) vs baseline while no significant improvements in cough frequency or
intensity in patients treated with Theophylline.
Significant improvements in cough intensity and frequency in patients treated with Acebrophylline compared
with baseline.
No ‘significant’ adverse events reported.
Randomised controlled trial, No
blinding
N=30
(20M/
10F)
Acebrophylline (200mg/d, syrup 10ml b.i.d.)
Theophylline (474mg/d, elixir 10ml tid) for 10 days.
Endpoints:
Cough (frequency/
intensity), Safety
Eligibility
criteria:
Patients
diagnosed with
bronchial
asthma
Asthma

35. A open-label study of COPD patients
100 mg acebrophylline, twice
daily for 14 days
Patients (N=30)
35
Improvement in cough intensity and frequency, auscultatory pattern, dyspnoea, cyanosis,
difficulty of expectoration by Short Course of Treatment with Acebrophylline in COPD
COPD
patients
Endpoints:
• Improvement in symptoms and signs such as
cough intensity and frequency, auscultatory
pattern, dyspnoea, cyanosis, difficulty of
expectoration, sputum quantity, appearance and
density, were evaluated at baseline and after
1,3,5, 7,10 and 14 days of therapy.
• The rheological properties of the bronchial mucus
(viscosity and spinnability) were measured and
respiratory function tests were performed before
and after treatment.
G Agliati.The Journal of International Medical Research 1996: 24: 302 - 310
There was a progressive improvement of all evaluated symptoms and signs, resulting in improvement of
the auscultatory pattern, as well as dyspnoea.
COPD

36. Acebrophylline is better choice than Theophylline in patients having
cardiovascular co-morbidity
• Treatment arms: Patients were randomized 1:1 to receive medications for 6 weeks
• Evaluation and Follow-up: Spirometric variables, symptomatic benefit and adverse effects were recorded on three
visits (day ‘0’, ‘21’ and ‘42’) x 6wks
Tapadar SR, Das M, Chaudhuri AD, Basak S, Mahapatra AB. J Clin Diagn Res. 2014 Sep;8(9):MC11-4.
Acebrophylline 100mg +18mcg Tiotropium inhalation
Theophylline 300mg SR +18mcg Tiotropium inhalation
Day 0 42
Design: Open randomized comparative
longitudinal study was conducted
Population: 40 moderate degree COPD
patients
21
Gp 2
Gp 1
Spirometric variables
Acebrophylline is better choice than Theophylline in patients having cardiovascular co-morbidity. Sustained release
Theophylline & Acebrophylline are both effective as add-on therapy with Tiotropium
COPD

37. Twice daily N-acetylcysteine 600 mg for exacerbations of COPD (PANTHEON):
a randomised, double-blind placebo-controlled trial
Placebo
NAC 600mg BD
Day 0 360
180
Primary end
point analysis
R
• Treatment arms: Patients were randomized 1:1 to receive medications or placebo for 12 months. Pts
stratified by ICS usage
• Evaluation and Follow-up: Exacerbation rate at end of 1 year
– time-to-first exacerbation and time-to-recurrent exacerbation
– number of patients with exacerbations requiring systemic corticosteroids or antibiotics, or use of shortacting
β2-agonist as rescue drug
Design: Prospective, randomised,
double-blind, placebo-controlled,
parallel-group study
Population: 1006 moderate-severe
COPD patients over a period of
one year
Zheng JP, Wen FQ, Bai CX, Wan HY, Kang J, Chen P et al; PANTHEON study group. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON):
a randomised, double-blind placebo-controlled trial. Lancet Respir Med. 2014 Mar;2(3):187-94
COPD

38. Results
Annual exacerbation rate
NAC reduces exacerbation rates by 22%
Zheng JP, Wen FQ, Bai CX, Wan HY, Kang J, Chen P et al; PANTHEON study group. Twice daily N-acetylcysteine 600 mg for
exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir
COPD

39. Addition of NAC to Acebrophylline in COPD
 A mild, significant attenuation in ozone-induced EBC-MDA increase after 4-
week treatment was observed with oral N-acetyl-cysteine in asthmatic
patients.
 NAC therefore might also reduce MDA levels in other pulmonary conditions
including COPD.
 Therefore, addition of NAC can be done in Acebrophylline in stable moderate
to severe COPD patients when there is increased oxidative stress measured by
parameters like ROS or MDA levels; this might help in reducing exacerbations
Bartoli ML, Novelli F, Costa F, et al. Malondialdehyde in exhaled breath condensate as a marker of oxidative stress in different pulmonary diseases. Mediators Inflamm.
2011;2011:891752. doi:10.1155/2011/891752

40. Overall role of Acebrophylline + NAC combination
No pre-clinical or clinical studies are available on the combination of Acebrophylline plus
NAC.

41. Guideline recommendations

42. Guideline recommendations
2022 COPD GOLD Guidelines:
• Regular treatment with mucolytics such as N-acetylcysteine & carbocysteine may reduce
exacerbations and modestly improve health status in patients not receiving ICS
2015 American College of Chest Physicians (ACCP)/Canadian Thoracic Society (CTS)
guidelines:
• Recommended N-acetylcysteine treatment for patients with moderate to severe COPD and a history
of two or more exacerbations during the previous 2 years
GOLD 2021. Available from: https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf . Accessed on 13th October 2021
Criner GJ, et al. Chest. 2015 Apr;147(4):894-942.

43. 2017: Prevention of COPD exacerbations: a European Respiratory Society/
American Thoracic Society guideline
 Mucolytic therapy- N-acetylcysteine, ambroxol or carbocisteine reduces likelihood of
hospitalization &, when given in high doses, may also reduce COPD exacerbations
 No effect on mortality was shown, although there were low numbers of deaths in
the trials to definitively determine the effect on mortality
 No evidence that mucolytic therapy increases adverse effects or alters quality of life.
ERS/ATS recommendation: For patients who have COPD with moderate or severe airflow obstruction &
exacerbations despite optimal inhaled therapy, suggest treatment with an oral mucolytic agent to prevent
future exacerbations
Wedzicha JA, et al. Eur Respir J. 2017;50(3):1602265

44. 2019 Canadian Thoracic Society Clinical Practice Guideline on pharmacotherapy in
patients with COPD
1B: Recommend oral N-acetylcysteine (600
mg po BID) for patients with chronic
bronchitis & high risk of AECOPD despite
optimal long-acting inhaled therapy
‡Oral Therapies-Roflumilast, N-
acetylcysteine, daily dose Azithromycin could
be considered with patients with high risk
AECOPD despite on optimal long-acting inhaled
therapy
Jean Bourbeau, et al. Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, DOI: 10.1080/24745332.2019.1668652

45. Stepwise approach recommended by the fifth edition of Japanese
Respiratory Society COPD guidelines
Japanese Respiratory Society. Guidelines for the Diagnosis and Treatment of COPD, 5th ed.; Japanese Respiratory Society: Tokyo,
Japan, 2018; Available online: https://www.jrs.or.jp/modules/guidelines/index.php?content_id=1

46. European Respiratory Society guidelines for bronchiectasis
 Long-term mucoactive treatment (⩾3 months) in adult patients with
bronchiectasis who have difficulty in expectorating sputum and poor
quality of life and where standard airway clearance techniques have
failed to control symptoms
Polverino E et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J 2017; 50: 1700629

47. Summary
 Inflammation and oxidative stress are involved in the pathogenesis
of chronic airway inflammatory diseases and closely correlate with
clinical outcomes
 They trigger excessive mucus production and secretion by glands
and goblet cells.
 Mucus Hypersecretion/ impaired mucociliary clearance occurs in
bronchitis, rhinosinusitis, otitis media with effusion, COPD, Asthma,
bronchiectasis, cystic fibrosis & lung cancer.
 Airway mucus hypersecretion if left untreated can lead to
exacerbations, poor prognosis and can seriously affect quality of life.

48. Summary
 Combination of Acebrophylline + NAC has bronchodilator, anti-inflammatory,
mucolytic and antioxidant properties
 There are evidences on role of NAC in mucus hypersecretion
 Sustained release Theophylline and Acebrophylline are both effective as add-
on therapy with Tiotropium (LAMA) in relieving symptoms as well as
improving spirometric parameters in moderate COPD patients.
 Acebrophylline is a better choice than Theophylline for COPD patients having
cardiovascular co-morbidity.
 Acebrophylline is also safer than SR Theophylline in respect of central nervous
system related side effects.

49. THANK YOU