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In India, 70% of the homes use biomass fuel for cooking and heating purposes in poorly ventilated kitchens, and the amount of particulate matter pollution generated by the burning of biomass fuel is extremely high. Ninety percent of rural households and 32% of urban households cook their meals on a biomass stove &lt;number&gt;
What&apos;s Hot in Nebs and Meds &lt;number&gt; The NHLBI/WHO guidelines for the diagnosis, treatment and management of COPD, otherwise known as the GOLD guidelines, outline approaches that define severity of disease by pulmonary function, FEV1, and symptoms. These guidelines then outline appropriate medial therapy for patients at each level of severity, in a cumulative fashion. All patients, starting at Stage I, or mild COPD, should have efforts to reduce risk factors, the primary issue here being smoking, influenza vaccine, and short-acting bronchodilators to use when needed. At Stage II, or moderate COPD, and above, regular treatment with one or more bronchodilators and rehabilitation should be added to the care regimen At Stage III, or severe COPD, and above, inhaled glucocorticosteriods should be added if patients have repeated exacerbations. At Stage IV, or very severe COPD, and above, long-term oxygen should be added if patients have chronic respiratory failure, and surgical options should be considered. BROVANA is an appropriate medicine to consider for patients with moderate and above COPD who are not adequately controlled with or who overuse SABAs.
Copd update 2015
Vice President UP Diabetes Association
Fellow UP Diabetes Association
Member Indian College Of Allergy Asthma & Immunology
Non communicable diseases are the biggest
cause of death worldwide
WHO Report 2011
63 % of deaths in 2008 were due
– Cardiovascular diseases (48%)
– Cancer (21%)
– Chronic Respiratory Diseases (12%)
– Diabetes (3%)
More deaths due to
CDs than NCDs
e.g. TB, Malaria,
Deaths due to CDs have
More people now die
due to NCDs
diseases e.g.COPD top
CDs: Communicable Diseases
NCDs: Non-Communicable Diseases
Scenario in India
JAPI 2012; 60 (Suppl):5-7
PRIOR TO 2004
• Chronic Bronchitis
Clinical diagnosis as chronic productive
cough for three months each in
two successive years.
Pathological diagnosis as the permanent
enlargement of the airspaces and destruction of the airways
Loss of function
Now first two of these (chronic bronchitis and emphysema)
are included under a single umbrella
Bronchodilators in COPD
Beta 2 Agonists
Short Acting Beta 2 agonists (SABA) Salbutamol
Long Acitng Beta 2 agonists (LABA) Formoterol
Short Acting Muscarinic Antagonist (SAMA) Ipratropium
Long Acting Muscarinic Antagonists (LAMA) Tiotropium,
SABA & SAMA for short term use in acute cases
LABA & LAMA for long term maintenance therapy
MABAs are a type of agent that have both
β2-agonist and anticholinergic activity in one
This is probably the group in which triple therapy may be very effective
Smoking is by far
recognized to be most important risk
factor for development of COPD
But smoking is not the only risk factor!
3 billion people exposed to biomass fuel
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
Non smokers reported greater lifetime burdens of respiratory
10-12% of individuals with COPD have never smoked
Indian Edition /Vol.4,No.1,2014
COPD in non smokers
• In INSEARCH phase II study, approximately
60% of chronic bronchitis patients were
• Respiratory symptoms were reported in 13%
of 3,608 nonsmoking women involved in
• 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%.
10-fold increased risk of chronic bronchitis and 17-fold increased risk of
• Alpha-1 antitrypsin deficiency and other genetic factors
COPD in non smokers:
25 years of COPD Management
Steroids alone with
LABA :salmeterol or
ICS alone or in
Salbutamol only need
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
• 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.
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.
• 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.
• 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.
• 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.
• 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
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.
• 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.
• 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.
• 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).
• 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
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.
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.
• 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).
• 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.
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.
• 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
• 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.
• 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.
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.
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-
• 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.
• 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
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=
• 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.
American Journal of Respiratory and Critical Care Medicine, Vol. 185, No. 3 (2012),
Vitamin D and Chronic Obstructive Pulmonary Disease: Justified Optimism or
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.