COPD is one of the commonest noncommunicable causes of death worldwide.

1. COPD Update
Dr.Veerendra Singh
Vice President UP Diabetes Association
Fellow UP Diabetes Association
Member Indian College Of Allergy Asthma & Immunology

2. Non communicable diseases are the biggest
cause of death worldwide
WHO Report 2011

3. 63 % of deaths in 2008 were due
to NCDs
– Cardiovascular diseases (48%)
– Cancer (21%)
– Chronic Respiratory Diseases (12%)
– Diabetes (3%)

4. Last 5-6
decades
Last 2
decades
More deaths due to
CDs than NCDs
e.g. TB, Malaria,
HIV/AIDs, Leprosy,
Dengue
Deaths due to CDs have
declined sharply
More people now die
due to NCDs
Chronic respiratory
diseases e.g.COPD top
this list
CDs: Communicable Diseases
NCDs: Non-Communicable Diseases
Scenario in India
JAPI 2012; 60 (Suppl):5-7

5. Global Strategy for Diagnosis, Management and Prevention of COPD
Burden of COPD
 COPD is a leading cause of morbidity and
mortality worldwide.
 The burden of COPD is projected to increase
in coming decades due to continued
exposure to COPD risk factors and the aging
of the world’s population.
© 2014 Global Initiative for Chronic Obstructive Lung Disease

6. Crude estimates suggest there are 30 million
COPD patients in India. [8] India contributes
the highest COPD mortality in the world
COPD Burden in India

7. Definition of COPD
© 2014 Global Initiative for Chronic Obstructive Lung Disease

8. PRIOR TO 2004
• Chronic Bronchitis
Clinical diagnosis as chronic productive
cough for three months each in
two successive years.
• Emphysema
Pathological diagnosis as the permanent
enlargement of the airspaces and destruction of the airways
• Asthma
Loss of function
ATS/ERS Guidelines
Now first two of these (chronic bronchitis and emphysema)
are included under a single umbrella
COPD

9. Global Strategy for Diagnosis, Management and Prevention of COPD
Definition of COPD
COPD, a common preventable and treatable
disease, is characterized by persistent airflow
limitation that is usually progressive and associated
with an enhanced chronic inflammatory response in
the airways and the lung to noxious particles or
gases.
© 2014 Global Initiative for Chronic Obstructive Lung Disease

10. Global Strategy for Diagnosis, Management and Prevention of COPD
Differential Diagnosis:
COPD and Asthma
COPD
• Onset in mid-life
• Symptoms slowly progressive
• Long smoking history
ASTHMA
• Onset early in life (often childhood)
• Symptoms vary from day to day
• Symptoms worse at night/early morning
• Allergy, rhinitis, and/or eczema also present
• Family history of asthma
© 2014 Global Initiative for Chronic Obstructive Lung Disease
Asthma patients frequently have symptom free periods but
COPD patient can never be asymptomatic

11. Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK

12. Global Strategy for Diagnosis, Management and Prevention of COPD
Mechanisms Underlying Airflow Limitation in
COPD
Small Airways Disease
• Airway inflammation
• Airway fibrosis
• luminal plugs
• Increased airway resistance
Parenchymal Destruction
• Loss of alveolar attachments
• Decrease of elastic recoil
AIRFLOW LIMITATION

13. Global Strategy for Diagnosis, Management and Prevention of
COPD
Risk Factors for COPD
Genes
Infections
Socio-economic
status
Aging Populations
© 2014 Global Initiative for Chronic Obstructive Lung Disease

14. Diagnosing COPD
© 2014 Global Initiative for Chronic Obstructive Lung Disease

15. Exposure to risk factore
Smoking
occupation dust and fumes
indoor/outdoor pollution
COPD
SPIROMETRY: Required to establish diagnosis
Global Strategy for Diagnosis, Management and Prevention of COPD
Diagnosis of COPD
²
© 2014 Global Initiative for Chronic Obstructive Lung Disease
Symptoms
shortness of breath
chronic cough
sputum production

16. Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of Airflow Limitation:
Spirometry
Spirometry should be performed after
the administration of an adequate dose of a
short- acting inhaled bronchodilator to
minimize variability.
A post-bronchodilator FEV1/FVC < 0.70
confirms the presence of airflow limitation.
© 2014 Global Initiative for Chronic Obstructive Lung Disease

17. Spirometry:
Normal Trace Showing FEV1 and FVC
1 2 3 4 5 6
1
2
3
4
Volume,liters
Time, sec
FVC5
1
FEV1 = 4L
FVC = 5L
FEV1/FVC = 0.8
© 2014 Global Initiative for Chronic Obstructive Lung Disease

18. Spirometry: Obstructive Disease
Volume,liters
Time, seconds
5
4
3
2
1
1 2 3 4 5 6
FEV1 = 1.8L
FVC = 3.2L
FEV1/FVC = 0.56
Normal
Obstructiv
e
© 2014 Global Initiative for Chronic Obstructive Lung Disease

19. Role of Chest X Ray in COPD
 Near normal except a
flat diaphragm and
increased
bronchovascular
markings
 Seldom diagnostic but
valuable to exclude
alternative diagnoses
and comorbidities.

20. Global Strategy for Diagnosis, Management and Prevention of COPD
Additional Investigations
Lung Volumes and Diffusing Capacity: Help to
characterize severity, but not essential to patient
management.
Oximetry and Arterial Blood Gases: evaluate oxygen
saturation and need for supplemental oxygen therapy.
Alpha-1 Antitrypsin Deficiency Screening: when COPD
develops in patients of Caucasian descent under 45
years or with a strong family history of COPD.
© 2013 Global Initiative for Chronic Obstructive Lung Disease

21. Severity of COPD
© 2014 Global Initiative for Chronic Obstructive Lung Disease

22. • Determine the severity of the disease, its
impact on the patient’s health status and
the risk of future events (for example
exacerbations) to guide therapy.
• Comorbidities occur frequently in COPD
patients, and should be actively looked for.
Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD: Goals
© 2014 Global Initiative for Chronic Obstructive Lung Disease

23. Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD
 Symptoms
 Degree of airflow limitation using
spirometry
 Risk of exacerbations
 Comorbidities
© 2014 Global Initiative for Chronic Obstructive Lung Disease

24. Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD symptoms
© 2014 Global Initiative for Chronic Obstructive Lung Disease
COPD Assessment Test (CAT)
or
Clinical COPD Questionnaire (CCQ)
or
mMRC Breathlessness scale

25. COPD Assessment Test (CAT): An 8-item measure of
health status impairment in COPD
Clinical COPD Questionnaire (CCQ): Self-administered
questionnaire developed to measure clinical control in
patients with COPD
Modified British Medical Research Council (mMRC)
Questionnaire:
Breathlessness Measurement, relates well to other measures
of health status and predicts future mortality risk.
Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of Symptoms
© 2014 Global Initiative for Chronic Obstructive Lung Disease

26. Global Strategy for Diagnosis, Management and Prevention of COPD
Modified MRC (mMRC)Questionnaire
mMRC Grade Symptoms
Grade 0. Breathless with strenuous exercise.
Grade 1. Breathless when hurrying on the level or walking up a slight hill.
Grade 2. Breathless when walking on own pace on the level.
Grade 3. Breathless after walking about 100 meters on the level.
Grade 4. Breathless with minimal exertion
© 2014 Global Initiative for Chronic Obstructive Lung Disease

27. Global Strategy for Diagnosis, Management and Prevention of COPD
Classification of Severity of Airflow
Limitation in COPD*
FEV1/FVC < 0.70
Post-Bronchodilator FEV1
GOLD 1: Mild FEV1> 80% predicted
GOLD 2: Moderate (<80%) 50% - 79% predicted
GOLD 3: Severe (<50%) 30% - 49% predicted
GOLD 4: Very Severe < 30% predicted
© 2014 Global Initiative for Chronic Obstructive Lung Disease

28. Global Strategy for Diagnosis, Management and Prevention of COPD
Combined Assessment of COPD
© 2014 Global Initiative for Chronic Obstructive Lung Disease
Exacerbation history
≥ 2 exacerbations
or
> 1 exacerbation
leading to hospital
admission
1
not leading to hospital
admission)
0
Symptoms
(C) (D)
(A) (B)
CAT < 10
Gold 4
Gold 3
Gold 2
Gold 1
CAT > 10
mMRC 0–1 mMRC > 2
No exacerbations
exacerbation
spirometricassessment

29. Indicators of high risk
 Two or more exacerbations within last year
 FEV1 < 50 % of predicted value
 Hospitalization for a COPD exacerbation
Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD
© 2014 Global Initiative for Chronic Obstructive Lung Disease

30. Therapeutic Options
© 2014 Global Initiative for Chronic Obstructive Lung Disease

31. Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Key Points
 Smoking cessation influences the natural
history of COPD.
 Regular physical activity should be
encouraged to remain active.
© 2014 Global Initiative for Chronic Obstructive Lung Disease

32.  Appropriate pharmacologic therapy can reduce
COPD symptoms, reduce the frequency and
severity of exacerbations, and improve health
status and exercise tolerance.
 None of the existing medications has been
shown to modify the long-term decline in lung
function.
 Influenza and pneumococcal vaccination should
be offered depending on local guidelines.
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Key Points
© 2014 Global Initiative for Chronic Obstructive Lung Disease

33. Bronchodilator medications are
central to the symptomatic
management of COPD
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Bronchodilators
© 2014 Global Initiative for Chronic Obstructive Lung Disease

34. Bronchodilators in COPD
Beta 2 Agonists
 Short Acting Beta 2 agonists (SABA) Salbutamol
,Terbutaline
 Long Acitng Beta 2 agonists (LABA) Formoterol
,Salmeterol,Indacaterol, Vilanterol
Anticholinergics
 Short Acting Muscarinic Antagonist (SAMA) Ipratropium
,Oxitropium
 Long Acting Muscarinic Antagonists (LAMA) Tiotropium,
Aclidinium, glycopyronnium,Umeclidinium)
SABA & SAMA for short term use in acute cases
LABA & LAMA for long term maintenance therapy

35. MABAs are a type of agent that have both
β2-agonist and anticholinergic activity in one
drug.

36. Long-acting inhaled bronchodilators reduce
exacerbations and related hospitalizations and
improve symptoms and health status.
Combining bronchodilators of different
pharmacological classes may improve efficacy and
decrease the risk of side effects.
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Bronchodilators
© 2013 Global Initiative for Chronic Obstructive Lung Disease

37. Inhaled Corticosteroids (ICS)

38.  Regular treatment with inhaled corticosteroids
improves symptoms, lung function and quality
of life and reduces frequency of exacerbations
for COPD patients with an FEV1< 60%
predicted.
 Inhaled corticosteroid therapy is associated
with an increased risk of pneumonia.
Global Strategy for Diagnosis, Management and Prevention of COPD
Inhaled Corticosteroids
© 2014 Global Initiative for Chronic Obstructive Lung Disease

39.  Chronic treatment with systemic
corticosteroids should be avoided
because of an unfavorable benefit-to-
risk ratio.
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Systemic
Corticosteroids
© 2014 Global Initiative for Chronic Obstructive Lung Disease

40. Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Theophylline
 Theophylline is less effective and less well
tolerated than inhaled long-acting
bronchodilators and is not recommended if
those drugs are available and affordable.
 Low dose theophylline reduces
exacerbations but does not improve post-
bronchodilator lung function.
© 2014 Global Initiative for Chronic Obstructive Lung Disease

41.  In patients with severe and very severe
COPD (GOLD 3 and 4) and a history of
exacerbations and chronic bronchitis, the
phospodiesterase-4 inhibitor, roflumilast,
reduces exacerbations.
Global Strategy for Diagnosis, Management and Prevention of COPD
Phosphodiesterase-4 Inhibitors
© 2014 Global Initiative for Chronic Obstructive Lung Disease

42. Influenza vaccines is recommended for
COPD patients 65 years and older and for
younger than age 65 with FEV1< 40%
predicted.
The use of antibiotics, other than for
treating infectious exacerbations of COPD
and other bacterial infections, is currently
not indicated.
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Other Pharmacologic
Treatments
© 2014 Global Initiative for Chronic Obstructive Lung Disease

43. Alpha-1 antitrypsin augmentation therapy:
not recommended for patients with
COPD that is unrelated to the genetic
deficiency.
Mucolytics:
Patients with viscous sputum may benefit
from mucolytics; overall benefits are very
small.
Antitussives: Not recommended.
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Other Pharmacologic
Treatments
© 2014 Global Initiative for Chronic Obstructive Lung Disease

44. Oxygen Therapy: The long-term administration of
oxygen (> 15 hours per day) to patients with
chronic respiratory failure.
Ventilatory Support: Combination of noninvasive
ventilation (NIV) with long-term oxygen therapy
may be of some use in a selected subset of
patients.
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Other Treatments
© 2014 Global Initiative for Chronic Obstructive Lung Disease

45. Stable COPD
© 2014 Global Initiative for Chronic Obstructive Lung Disease

47. Exacerbationsperyear
0
CAT < 10
mMRC 0-1
GOLD 4
CAT >10
mMRC >2
GOLD 3
GOLD 2
GOLD 1
SAMA prn
or
SABA prn
LABA
or
LAMA
ICS + LABA
or
LAMA
Global Strategy for Diagnosis, Management and Prevention of COPD
Manage Stable COPD: PharmacologicTherapy
RECOMMENDED FIRST CHOICE
A B
DC
ICS + LABA
and/or
LAMA
© 2014 Global Initiative for Chronic Obstructive Lung Disease
2 or more
or
> 1 leading
to hospital
admission
1 (not leading
to hospital
admission)

48. • FEV1/FVC < 0.70
• FEV1 ≥ 80% predicted
• FEV1/FVC < 0.70
• ≤ FEV1 50-80%
predicted
• FEV1/FVC < 0.70
• ≤ FEV1 30- 50%
predicted
• FEV1/FVC < 0.70
• FEV1 < 30% predicted
or FEV1 < 50%
predicted plus chronic
respiratory failure
Add regular treatment with long-acting bronchodilators; Begin Pulmonary
Rehabilitation
Add inhaled glucocorticosteroids if repeated acute
exacerbations
Add LTOT for chronic
hypoxemia.
Consider surgical
options
III: SevereI: Mild
II: Moderate
IV: Very Severe
Active reduction of risk factor(s); smoking cessation, flu vaccination
Add short-acting bronchodilator (as needed)
GOLD Guidelines

49. Comorbidities
© 2014 Global Initiative for Chronic Obstructive Lung Disease

50. Global Strategy for Diagnosis, Management and Prevention of COPD
COPD Comorbidities
• Cardiovascular diseases
• Osteoporosis
• Respiratory infections
• Anxiety and Depression
• Diabetes
• Lung cancer
• Bronchiectasis
© 2014 Global Initiative for Chronic Obstructive Lung Disease

51. In general, presence of comorbidities should
not alter COPD treatment and comorbidities
should be treated as if the patient did not have
COPD.
Global Strategy for Diagnosis, Management and Prevention of COPD
ManageComorbidities
© 2014 Global Initiative for Chronic Obstructive Lung Disease

52. Cardiovascular diseases (ischemic heart
disease, heart failure, atrial fibrillation, and
hypertension) are major comorbidity in
COPD. Benefits of cardioselective beta-
blocker treatment in heart failure outweigh
potential risk even in patients with severe
COPD.
Global Strategy for Diagnosis, Management and Prevention of COPD
ManageComorbidities
© 2014 Global Initiative for Chronic Obstructive Lung Disease

53. Exacerbations
© 2014 Global Initiative for Chronic Obstructive Lung Disease

54.  The most common causes of COPD
exacerbations are viral upper respiratory
tract infections and infection of the
tracheobronchial tree.
 The goal of treatment is to minimize the
impact of the current exacerbation and to
prevent the development of subsequent
exacerbations.
Global Strategy for Diagnosis, Management and Prevention of COPD
Manage Exacerbations: Key Points
© 2014 Global Initiative for Chronic Obstructive Lung Disease

57. Prevention of exacerbations
 Quit smoking
 Long acting broncodilators
 Inhaled corticosteroids
 Pneumococcal and influenza vaccine
 PDE-4 inhibitors: Roflumilast
 Maintenece of physical activity
 Managing comorbidities
© 2014 Global Initiative for Chronic Obstructive Lung Disease

58. Asthma COPD Overlap
© 2014 Global Initiative for Chronic Obstructive Lung Disease

59. This is probably the group in which triple therapy may be very effective

60. Smoking is by far
recognized to be most important risk
factor for development of COPD

61. But smoking is not the only risk factor!
Biomass smoke
Occupational exposure
Outdoor pollution
3 billion people exposed to biomass fuel
worldwide
Long-term exposure to ambient air pollutants
increased the risk of COPD by 2-fold
Eur J Epidemiol 2003; 18: 45-53 , JAPI 2012; 60 (Suppl):5-7

62. Non smokers reported greater lifetime burdens of respiratory
disease
10-12% of individuals with COPD have never smoked
Indian Edition /Vol.4,No.1,2014

63. COPD in non smokers
• In INSEARCH phase II study, approximately
60% of chronic bronchitis patients were
nonsmokers.
• Respiratory symptoms were reported in 13%
of 3,608 nonsmoking women involved in
domestic cooking.

64. • Mosquito coil
One mosquito coil emitts particulate matter equivalent to those with
around 100 cigarettes
• Pulmonary tuberculosis
Prevalence of airflow obstruction varies from 28 to 68%.
• Asthma
10-fold increased risk of chronic bronchitis and 17-fold increased risk of
emphysema
• Alpha-1 antitrypsin deficiency and other genetic factors
COPD in non smokers:
Other causes

65. 25 years of COPD Management
1990-2015
1990s:
 Salbutamol
 Theophyllin
 Steroids alone with
salbutamol
 LABA :salmeterol or
formeterol
 anticholinergics
2015:
 Anticholinergics
 LABA
 SR Theophyllin
 ICS alone or in
combination with
LABA
 Salbutamol only need
based

66. Glimpses of new researches in COPD

67. Dual bronchodilation vs an ICS-LABA
in milder patients in patients with more severe disease
Both studies showed that LABA/LAMA seems to be more efficient than
the LABA-ICS combinations.

68. Long term prophylactic antibiotics

69. Cochrane Database Syst Rev. 2013 Nov 28;11:CD009764.
Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).
Herath SC1, Poole P.
• Seven RCTs involving 3170 patients were included in this systematic review. All
studies were published between 2001 and 2011.
• The antibiotics investigated were azithromycin, erythromycin, clarithromycin and
moxifloxacin.
• With use of continuous prophylactic antibiotics the number of patients
experiencing an exacerbation was reduced (odds ratio (OR) 0.55; 95% confidence
interval (CI) 0.39 to 0.77, 3 studies, 1262 participants, high quality).
• Use of continuous prophylactic antibiotics results in a clinically significant benefit
in reducing exacerbations in COPD patients. All trials of
continuous antibiotics used macrolides hence the noted benefit applies only to the
use of continuous macrolide antibiotics. The impact of pulsed antibiotics remains
uncertain and requires further research.The
Use of continuous prophylactic antibiotics results in a
clinically significant benefit in reducing exacerbations
in COPD patients.

70. Respir Med. 2013 Sep;107(9):1385-92. doi: 10.1016/j.rmed.2013.05.004. Epub 2013 Jun 12.
A meta-analysis on the prophylactic use of macrolide antibiotics for the prevention
of disease exacerbations in patients with Chronic Obstructive Pulmonary Disease.
Donath E1, Chaudhry A, Hernandez-Aya LF, Lit L.
• INTRODUCTION:
• Macrolides are of unique interest in preventing COPD exacerbations because they possess a variety of antibacterial, antiviral and anti-inflammatory
properties. Recent research has generated renewed interest in prophylactic macrolides to reduce the risk of COPD exacerbations. Little is known about
how well these recent findings fit within the context of previous research on this subject. The purpose of this article is to evaluate, via exploratory meta-
analysis, whether the overall consensus favors prophylactic macrolides for prevention of COPD exacerbations.
• METHODS:
• EMBASE, Cochrane and Medline databases were searched for all relevant randomized controlled trials (RCTs). Six RCTs were identified. The primary
endpoint was incidence of COPD exacerbations. Secondary endpoints including mortality, hospitalization rates, adverse events and likelihood of having at
least one COPD exacerbation were also examined.
• RESULTS:
• There was a 37% relative risk reduction (RR = 0.63, 95% CI: 0.45-0.87, p value = 0.005) in COPD exacerbations among patients taking macrolides compared
to placebo. Furthermore, there was a 21% reduced risk of hospitalization (RR = 0.79, 95% CI: 0.69-0.90, p-value = 0.01) and 68% reduced risk of having at
least one COPD exacerbation (RR = 0.34, 95% CI 0.21-0.54, p-value = 0.001) among patients taking macrolides versus placebo. There was also a trend
toward decreased mortality and increased adverse events among patients taking macrolides but these were not statistically significant.
• CONCLUSIONS:
• Prophylactic macrolides are an effective approach for reducing incident COPD exacerbations. There were several limitations to this study including a lack
of consistent adverse event reporting and some degree of clinical and statistical heterogeneity between studies
There was a 37% relative risk reduction (RR = 0.63, 95% CI: 0.45-0.87,
p value = 0.005) in COPD exacerbations among patients taking
macrolides compared to placebo. Furthermore, there was a 21%
reduced risk of hospitalization

71. PLoS One. 2015 Mar 26;10(3):e0121257. doi: 10.1371/journal.pone.0121257. eCollection 2015.
Prophylactic use of macrolide antibiotics for the prevention of chronic obstructive pulmonary disease
exacerbation: a meta-analysis.
Ni W1, Shao X1, Cai X1, Wei C1, Cui J1, Wang R2, Liu Y1.
• BACKGROUND:
• Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality.
Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties. Since the occurrence of AECOPDs is
associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach
towards the prevention of AECOPDs.
• METHODS:
• We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the
effect of prophylactic macrolide therapy on the prevention of AECOPDs. The primary outcomes were the total number of patients with one or more
exacerbations as well as the rate of exacerbations per patient per year.
• RESULTS:
• Nine RCTs comprising 1666 patients met the inclusion criteria. Pooled evidence showed macrolides could reduce the frequency of exacerbations in
patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01).
Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective. Moreover, among studies with 6-12
months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates. The overall
number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups. A tendency for
more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049).
• CONCLUSIONS:
• Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients
with COPD. However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance. A recommendation for
the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages.
6-12 months erythromycin or azithromycin therapy could
effectively reduce the frequency of exacerbations in patients
with COPD

72. N-Acetyl Cystein in COPD

73. Int J Chron Obstruct Pulmon Dis. 2014 Aug 6;9:825-36. doi: 10.2147/COPD.S51057. eCollection 2014.
Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine
in chronic obstructive pulmonary disease.
Tse HN1, Tseng CZ1.
N-acetylcysteine (NAC) is a mucolytic agent with both antioxidant and anti-inflammatory
properties. This paper also reviews the use of NAC in patients with COPD, especially the dose-
dependent properties of NAC, eg, its effects on lung function and the exacerbation rate in
patients with the disease. Earlier data from BRONCUS (the Bronchitis Randomized on NAC Cost-
Utility Study) did not suggest that NAC was beneficial in patients with COPD, only indicating that
it reduced exacerbation in an "inhaled steroid-naïve" subgroup. With regard to the dose-
dependent properties of NAC, two recent randomized controlled Chinese trials suggested that
high-dose NAC (1,200 mg daily) can reduce exacerbations in patients with COPD, especially in
those with an earlier (moderately severe) stage of disease, and also in those who are at high risk
of exacerbations. However, there was no significant effect on symptoms or quality of life in
patients receiving NAC. Further studies are warranted to investigate the effect of NAC at higher
doses in non-Chinese patients with COPD.
High-dose NAC (1,200 mg daily) can reduce
exacerbations in patients with COPD, especially in those
with an earlier (moderately severe) stage of disease, and
also in those who are at high risk of exacerbations.

74. Statins in COPD

75. Int J Clin Pract. 2008 Sep;62(9):1373-8.
Statins may reduce episodes of exacerbation and the requirement for intubation in patients
with COPD: evidence from a retrospective cohort study.
Blamoun AI1, Batty GN, DeBari VA, Rashid AO, Sheikh M, Khan MA.
• This is a retrospective cohort study of 185 patients with COPD exacerbation, with a 1-year follow-up. Outcomes examined
were repeat hospitalisation and intubations for COPD exacerbation. Baseline characteristics for which the p-value was < or =
0.10 were considered as covariates for inclusion in a multivariate model.
• RESULTS:
• The statin group had fewer episodes of exacerbation and required intubation fewer times than the subjects not
receiving statins (p < 0.0001 for both outcomes). Unadjusted odds ratios (OR) for no statin use vs. statin use were 9.54 (95%
CI: 4.54-20.02) for exacerbation and 10.47 (CI: 4.56-24.01) for intubation. The OR, adjusted for the use of angiotensin-
converting enzyme inhibitors or angiotensin receptor blockers (ORa), were 2.35 (CI: 1.01-5.50) for non-statin users
exhibiting an exacerbation and 10.36 (CI: 2.77-38.76) for this group requiring intubation, compared with statin users.
Similarly, ORa for long-acting beta(2) agonists as a covariate were 3.01 (CI: 1.46-6.10) for exacerbation and 8.89 (CI: 3.67-
21.32) for intubation. Time to outcome during the observation period was reduced by statins with the hazard ratio (HR) for
exacerbation of 0.19 (CI: 0.06-0.14); HR for statins reducing intubation was 0.14 (95% CI: 0.10-0.30).
• CONCLUSIONS:
• These data suggest that the use of statins may be associated with lower incidence of both exacerbations and
intubations in patients with COPD.
These data suggest that the use of statins may be
associated with lower incidence of both exacerbations and
intubations in patients with COPD.

76. Chest. 2009 Sep;136(3):734-43. doi: 10.1378/chest.09-0194. Epub 2009 Apr 17.
Statins in COPD: a systematic review.
Janda S1, Park K, FitzGerald JM, Etminan M, Swiston J.
• The 3-hydroxy 3-methylglutaryl coenzyme A reductase inhibitors (ie, statins) are widely used for the treatment of patients with
hypercholesterolemia and cardiovascular disease. Emerging evidence suggests a beneficial effect of statins on the morbidity and mortality
of patients with COPD. The objective of this study was to perform a systematic review of the literature evaluating the effect of statin therapy
on outcomes in patients with COPD.
• METHODS:
• Medline, Excerpta Medica Database, PapersFirst, and the Cochrane collaboration and Cochrane Register of controlled trials were searched.
Randomized controlled trials (RCTs), observational cohort studies, case-control studies, and population-based analyses were considered for
inclusion.
• RESULTS:
• Nine studies were identified for review (four retrospective cohorts, one nested case-control study of a retrospective cohort, one
retrospective cohort and case series, two population-based analyses, and one RCT). All studies showed a benefit from statin therapy for
various outcomes in COPD patients, including the number of COPD exacerbations (n = 3), the number of and time to COPD-related
intubations (n = 1),pulmonary function (eg, FEV(1) and FVC) [n = 1], exercise capacity (n = 1), mortality from COPD (n = 2), and all-cause
mortality (n = 3). No studies describing a negative or neutral effect from statin therapy on outcomes in COPD patients were identified.
• CONCLUSIONS:
• The current literature collectively suggests that statins may have a beneficial role in the treatment of COPD. However, the majority of
published studies have inherent methodological limitations of retrospective studies and population-based analyses. There is a need for
prospective interventional trials designed specifically to assess the impact of statins on clinically relevant outcomes in COPD.
The current literature collectively suggests that statins may
have a beneficial role in the treatment of COPD.

77. Beta Blockers in COPD

78. PLoS One. 2014 Nov 26;9(11):e113048. doi: 10.1371/journal.pone.0113048. eCollection 2014.
Beta-blockers reduced the risk of mortality and exacerbation in patients with COPD: a meta-
analysis of observational studies.
Du Q1, Sun Y1, Ding N1, Lu L1, Chen Y1.
• An extensive search of the EMBASE, MEDLINE and Cochrane was performed to retrieve the
studies of beta-blockers treatment in patients with COPD. The random effects model meta-
analysis was used to evaluate effect on overall mortality and exacerbation of COPD.
• Fifteen original observational cohort studies with a follow-up time from 1 to 7.2 years were
included. The results revealed that beta-blockers treatment significantly decreased the risk of
overall mortality and exacerbation of COPD. The relative risk (RR) for overall mortality was 0.72
(0.63 to 0.83), and for exacerbation of COPD was 0.63 (0.57 to 0.71). In subgroup analysis
of COPD patients with coronary heart disease or heart failure, the risk for overall mortality was
0.64 (0.54-0.76) and 0.74 (0.58-0.93), respectively.
• The findings of this meta-analysis confirmed that beta-blocker use in patients
with COPD may not only decrease the risk of overall mortality but also reduce the
risk of exacerbation of COPD. Beta-blocker prescription for cardiovascular diseases
needs to improve in COPD patients.
Beta-blocker use in patients with COPD may not only
decrease the risk of overall mortality but also reduce the risk
of exacerbation of COPD.

79. Ann Pharmacother. 2004 Jan;38(1):142-5.
Use of beta-blockers in patients with COPD.
Andrus MR1, Holloway KP, Clark DB.
• To evaluate the safety and cardiovascular benefits of beta-blocker therapy in patients
with chronic obstructive pulmonary disease(COPD).
• DATA SOURCES:
• Clinical literature was accessed through MEDLINE (1966-February 2003). Key search
terms included chronic obstructive pulmonary disease and adrenergic beta-
antagonists.
• DATA SYNTHESIS:
• beta-Blockers are often avoided in patients with COPD because of fear of
bronchoconstriction, despite the known cardiovascular mortality benefits. A review of
studies evaluating the use of beta-blockers in COPD was undertaken.
• CONCLUSIONS:
• The literature supports the safety and mortality benefits of using beta-blockers
in COPD. Patients with mild to moderate COPDshould receive cardioselective
beta-blocker therapy when a strong indication exists.
The literature supports the safety and mortality benefits of using
beta-blockers in COPD. Patients with mild to moderate COPD
should receive cardioselective beta-blocker therapy when a strong
indication exists.

80. Vit.D Deficiency in COPD

81. Respir Res. 2014 Dec 13;15(1):131. doi: 10.1186/s12931-014-0131-0.
Severe vitamin D deficiency is associated with frequent exacerbations and
hospitalization in COPD patients.
Malinovschi A1, Masoero M2, Bellocchia M3, Ciuffreda A4, Solidoro P5, Mattei A6, Mercante L7, Heffler E8, Rolla G9, Bucca C10.
• Serum vitamin D (25-hydroxyvitamin D) levels were measured in 97 COPD patients and
related to lung function, comorbidities, FEV1 decline, AECOPD and hospital admission during
the previous year.
• Most patients (96%) had vitamin D deficiency, which was severe in 35 (36%). No significant
relationship was found between vitamin Dand FEV1 or annual FEV1 decline. No difference
between patients with and without severe vitamin D deficiency was found in age, gender,
BMI, smoking history, lung function, and comorbidities, apart from osteoporosis (60.9% in
severe deficiency vs 22.7%, p=0.001). In multiple logistic regression models, severe
deficiency was independently associated with AECOPD [adjusted odds ratios (aOR) of 30.5
(95% CI 5.55, 168), p<0.001] and hospitalization [aOR 3.83 (95% CI 1.29, 11.4), p=0.02]. The
odds ratio of being a frequent exacerbator if having severe vitamin Ddeficiency was 18.1
(95% CI 4.98, 65.8) (p<0.001), while that of hospitalization was 4.57 (95% CI 1.83, 11.4) (p=
0.001).
• In COPD patients severe vitamin D deficiency was related to more
frequent disease exacerbations and hospitalization.
In COPD patients severe vitamin D deficiency was related
to more frequent disease exacerbations and hospitalization.

82. American Journal of Respiratory and Critical Care Medicine, Vol. 185, No. 3 (2012),
Vitamin D and Chronic Obstructive Pulmonary Disease: Justified Optimism or
False Hope?
Seif O. Shaheen Ph.D. , and Adrian R. Martineau Ph.D.
•Data from observational studies are conflicting, both from studies of patients
with COPD and from population-based research.
•A recent cross-sectional study observed a positive association between 25(OH)D
concentrations and FEV1 in patients with COPD (12). In contrast, a longitudinal
study of continuous smokers with COPD found no difference in baseline 25(OH)D
concentrations between individuals who had a rapid decline in lung function and
those with a slow decline
•To date, population-based data on the relation of 25(OH)D to lung function
decline are lacking, although preliminary data, reported in the form of an
abstract, have suggested a possible relation between lower vitamin D status and
faster decline in the FEV1/FVC ratio (but not FEV1) in an elderly population (16).
To date, population-based data on the relation of 25(OH)D to lung
function decline are lacking, although preliminary data suggested a
possible relation between lower vitamin D status and faster decline in
the FEV1/FVC ratio (but not FEV1) in an elderly population.

84. Take Home Messages

85. 85
Instead of COPD
controlling our patient,
Remember
allow our patient to
control his COPD

86. Thank You