Transcript COPD PHENOTYPES - Indian Chest Society

ICS-Dr. S.N. Tripathy Oration.
"PHENOTYPES IN COPD.
WHAT IS NEW?"
Prof.(Dr.) Pranab Baruwa
MBBS,DTCD,MD(TB&Chest Dis.),
MNAMS(Resp.Med.) Fellow ICS
Trained in USA as WHO Fellow.
Formerly :
Prof. & Head, Dept. of TB & Chest Dis. Gauhati Medical College,. Guwahati.
Principal cum Chief Superintendent, Tezpur Medical College, Tezpur.
Principal cum Chief Superintendent, Assam Medical College, Dibrugarh.
Dean, Faculty of Medicine, Dibrugarh University, Dibrugarh.
President,Indian Chest Society 2010-2011
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
COPD is a “preventable and treatable disease state
characterized by airflow limitation that is not fully
reversible. It is usually progressive and
is
associated with an abnormal inflammatory response
of the lung to noxious particles or gases”.
Exacerbations and co morbidities contribute to the
overall severity in individual patients.
COPD is a leading cause of morbidity and mortality
globally. It is on the rise.
On average, 10% of adult worldwide have COPD.
Pawels RA, Buist AS et al Am J Respir Crit Care Med. 2001. 163: 1256-1276
Celli BR, Mac Nee W. Eur Resp J. 2004.23:932-946
Buist AS, Meburnie MA. et.al. Lancet 2007.370:741-750
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
 The Predominant risk factor for COPD is cigarette
smoking.
 The relationship between smoking and COPD is not
absolute.
 COPD can occur in lifelong non-smokers.
 More than 15% of subjects worldwide who die from
COPD are non-smokers.
 Less than 30% of subjects with significant smoking
history develop COPD.
 Several factors influence in the development of
COPD- inhaled gases & particles, Genetics, health in
early life, Nutrition, Gender, Socio-economic status,
BMI etc.
Lawlor DA., Ebrahim S.et.al. Thorax 2005,60:851-858.
Silverman EK. Med. Clin North Am. 1996,80:501-522.
A Lakke PL., Scharling H. et.al. Thorax.2006:61:935-939
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Decline in Lung Function
 In non smokers FEV1 declines at the rate of 20-30 ml/yr
in adult.
 In most smokers FEV1 declines at the rate of 30-45
ml/yr
 In Susceptible/ COPD persons FEV1 declines at the rate
of 80-100 ml/yr.
David AL & Silverman EK. Respir Res 2001,2:20-26
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
 Response to treatment in different COPD
Patient is not same.
 Clinical presentation, pathological/ radiological
findings and even prognosis are different.
 Likely to be a group of heterogeneous disorders
J A Wedzicha Thorax 2000;55:631-632
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
How to define prognosis?
 COPD severity measured by forced expiratory volume in
1 second (FEV1) alone does not recognise
pathophysiological abnormalities in this heterogeneous
condition.
 Several indexes has been developed over the time to
explain the prognosis of COPD with limited benefit
 BODE index(BMI, FEV1, dyspnoea and exercise capacity)
 ADO index (age, dyspnoea, FEV1)
 DOSE index (dyspnoea, FEV1, smoking, and
exacerbation frequency)
Celli BR., Cote CG et.al. N. Engl. J. Med 2004:350:1005-1012
Puhan MA., Garcia–Aymerich J. et.al. Lancet 2009:374:704-711
Jones RC., Donalson G.C. et.al. Am J Respir Crit Care Med.2009:180:1189-1195
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
 All patients do not respond equally to all drugs.
 The need to identify “responders” to a particular
therapeutic intervention is crucial.
 Thus the concept of a clinical phenotype in COPD
has emerged.
 Phenotyping in COPD is a relatively young endeavor
as compared to many other fields.
 A MEDLINE search revealed just over 400
Phenotyping papers published in COPD, compared
to more than 5000 in breast cancer.
Respiratory Research 2009:10-41.
MeiLan K. Han, Agusti A. et.al. Am J Respir Crit Care Med. Med.2010:182:598-604.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Evolving concept of phenotype
 Historically, Dornhorst in 1955 for the first time
described two clinical phenotypes of COPD- the
classic ‘Blue Bloaters’ & ‘Pink Puffers’.
 The classic 'Blue Bloater' was described
as a younger patient with chronic
bronchitis, who often presented with
congestive right heart failure.
 The classic 'Pink Puffer' was an older
and skeletal muscle-wasting patient who
had unrelenting, disabling dyspnea and
clear evidence of emphysema.
Dornhorst AC Lancet 1955:1:1185-1187
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Evolving concept of phenotype
There are several other diseases where management
revolves around phenotypes e.g. In Breast cancer, presence of Estrogen & Progesterone
receptors within the tumour determines response to
therapy.
 In Asthma- cellular phenotypes of asthma
(Eosinophilic,Neutrophilic & pauci granulocytic) were
use to direct successful application of Mepolizumab (anti
IL-5) therapy
 In COPD, Roflumilast was initially tried in a general
COPD patients without much benefit. However, a sub
population of COPD patients with FEV1 <50% predicted,
chronic cough and sputum production demonstrated
greatest clinical response.
Rakha EA,Ellis IO Pathology:2009:41:40—47 Wenzel SE.N. Engl.J.Med.2009:360:1026—1028
Meilan K Han.Augusti A. et. al. Amer.J. Resp. and Crit.Care Med.2010:182:598—604.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
 The classic definition of Phenotype is “the
observable structural and functional characteristics
of an organism determined by its genotype and
modulated by its environment’’.
 An international group of experts has defined COPD
phenotype as “a single or combination of disease
attributes that describe differences between
individuals with COPD as they relate to clinically
meaningful outcomes (symptoms, exacerbations,
response to treatment, speed of progression of the
disease or death)”
Rice JP., Saccone NL. et.al. Adv. Genet 2001:42:69-76.
Han M.K., Augusti A. et. al. Amer.J. Resp & Crit care Med 2010 :182 598-604.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Han MK et.al. have suggested that clinical phenotypes
in COPD should1. Have predictive value
2. Be prospectively validated for each of the out comes
to which they may relate
3. Be able to classify patients into distinct subgroups
that provide prognostic information thereby help us
to determine the most appropriate therapy.
Han M.K., Augusti A. et. al. Amer.J. Resp & Crit care Med 2010 :182 598-604.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
 Proportional Venn diagram of OLD in the United
States (NHANES III surveys from 1988 to 1994) and
United Kingdom (GPRD 1998) for all ages.
Soriano JB, Davis KJ. et.al. CHEST 2003; 124:474–481
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
 Proportional Venn diagram of OLD in the United
States (NHANES III surveys from 1988 to 1994) and
United Kingdom (GPRD 1998) for all ages.
Soriano JB, Davis KJ et al.CHEST 2003; 124:474–481
ICS-Dr. S.N. Tripathy Oration.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Various studies have identified several clinical
phenotypes in COPD
Casanova C ., Cole C. et al Am. J Resp crit care med.2005:171:591-597
Kitagushi Y., Fujimoto k. et al. Resp. Med. 2006 100: 1742-1752
Makita H. Nasuhara Y. et al. Thorax 2007:62:932-937
Marsh SE, Travers J. et al Thorax 2008:63:761-767
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Burgel PR. Paillsseur J.I et al. Eur.Resp.Jour. 2010: 36:531-539.
Hurst J.R, Vestbo J. et al. N.Engl. J. Med. 2010: 363: 1128-1138.
Jo KW, Ra SW et al. Int. J. Tuber.Lung.Dis. 2010:.14:1481-1488.
Garcia Aymerich J., Gomez FP. et al. Thorax 2011:66:430-437.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Based on a series of factors, majority of the
studies have identified distinguished 3-5 Phenotypes in
COPD.
ICS-Dr. S.N. Tripathy Oration.
ICS-Dr. S.N. Tripathy Oration.
ICS-Dr. S.N. Tripathy Oration.
ICS-Dr. S.N. Tripathy Oration.
 MeiLan K Han et al stated that phenotype classically
refers to any observable characteristic of an organism,
and up until now, multiple disease characteristics have
been termed COPD phenotypes.
 Proposed the following variation on COPD definition: “a
single or combination of disease attributes that
describe differences between individuals with COPD as
they relate to clinically meaningful outcomes
(symptoms, exacerbations, response to therapy, rate of
disease progression, or death).”
 This more focused definition allows for classification of
patients into distinct prognostic and therapeutic
subgroups for both clinical and research purposes.
ICS-Dr. S.N. Tripathy Oration.
Characteristics of COPD phenotypes
Classified according to HRCT findings
 A total of 172 patients with stable COPD (FEV1<80%)
were examined by chest HRCT.
 Emphysematous changes and bronchial wall
thickening (BWT) were evaluated visually.
 COPD patients were classified into three phenotypes:
absence of emphysema, with little emphysema with or
without bronchial wall thickening (A phenotype),
emphysema without bronchial wall thickening (E
phenotype), and emphysema with bronchial wall
thickening phenotype (M phenotype).
 Morphological phenotypes of COPD show several
clinical characteristics.
 Different responsiveness to treatment with
bronchodilators and ICS to different Phenotypes.
Fusimoto K., Kitaguchi Y. et.al Respirology 2006:11:731-740
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Garcia Aymerich et.al in the Phenotypic
Characterization and Course of COPD (PAC-COPD) study
recruited 342 patients with COPD at their 1st
hospitalization and followed them for 4 years. 3 different
COPD Phenotypes were indentified and prospectively
validated : Severe respiratory COPD, Moderate
respiratory COPD and Systemic COPD.
Garcia. Aymerich J., Federico P. et.al Arch. Bronconeumol 2009:45(1)4-11.
Garcia Aymerich J., Gomez F.D. et.al Thorax 2010 doi:10:1136/thx.2010:15:44-84.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Study of COPD Phenotypes by using Principal
Component and cluster analysis.
Burgel et.al defined 4 different clinical phenotypes,
different from GOLD classification. Patients with
comparable airflow limitation (FEV1) belonged to different
phenotypes, had marked differences in symptoms, comorbidities and predicted mortality.
Burgel P.R., Pailaseur J.L. et.al Eur. Respir J., 2010:36:531-539.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Proportional classification of COPD Phenotypes
Marsh et.al defined 3 phenotypic subgroups in a study
on 96 COPD patients
1. 18/96 subjects (19%) had classical phenotypes of
chronic bronchitis and/or emphysema but no asthma.
2. 53/96 (55%) COPD patients asthma was the
predominant COPD phenotype.
3. 25/96 (26%) COPD patients had no classical asthma,
chronic bronchitis or emphysema.
Marsh SE., Travers J. et.al Thorax 2008:63:761-767.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
According to Marc Miravitlles et.al. among all phenotypes
described, there are 3 principal phenotypes that are
associated with distinct clinical, prognostic and different
therapeutic response to currently available therapies.
(1)“Overlap” or mixed COPD-asthma phenotype
(2) Exacerbator phenotype and
(3) Emphysema hyperinflation phenotype
Miravitlles M. Myriam Calle et.al. Arch Bronconeumol. 2012;48:86-98.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Other Phenotypes

Other phenotypes have been defined, but these
have very little clinical significance.

“Fast decliner”- a patient who suffers a loss of
lung function, expressed by FEV1, faster than
average. To identify this phenotype a strict followup of the lung function for at least 2 years is
required, no specific treatment has been identified
for this type of patients.
Rapid decline in FEV1 is predictive of morbidity,
mortality and hospitalization rates.

Celli BR., Thomas NE. et.al. Amer J. Respir Crit Care Med. 2008:178:331-338.
Wise RA. Am J. Med. 2006:119:4-11.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Other Phenotypes
 Chronic bronchitis phenotypes, defined as cough
and expectoration for at least 3 months of the year
for 2 consecutive years. This phenotype is usually
associated with airway disease, which can be
visualized
with
high-resolution
computed
tomography (HRCT).
 Chronic bronchitis can accompany any of the three
phenotypes.
 COPD patients with chronic bronchitis are younger,
more commonly men, more likely to be current
smoker, more symptomatic and have more frequent
comorbidities.
Am. Thora. Society. Amer J. Respir Crit Care Med. 1995:152:77-121
Victor Kim, Mailan K. Hans et.al. Chest 2011:140:626-633.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Other Phenotypes
Bronchiectasis phenotypes.
 Martinez-Garcia and Collegues in a series on 91
Spanish patients with well characterized, clinically
stable-moderate to severe COPD patients have
shown 57.6% to have Bronchiectasis on HRCT. They
were associated with severe airflow obstruction,
isolation of potentially pathogenic micro organism
(PPM) from sputum and at least one hospitalization
for COPD exacerbations in the previous year.
 In the East London COPD study 50% of patients with
COPD had Bronchiectasis.
 29% of patients with COPD in primary care in U.K.
were reported to have Bronchiectasis.
Martínez-García MA , Soler-Cataluña JJ, et al Chest . 2011 ; 140 ( 5 ): 1130 - 1137 .
Garcia-aymerich J., Gomez FP. et.al. Thorax 2011:66:432-437 O’Brien C, Guest PJ. et.al. Thorax
2000:55:635-642. Bafadhal M.Umar I. et.al. chest 2011:140:634-642
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Other Phenotypes

A systemic phenotype has also been defined in
patients who present obesity, cardiovascular disease,
diabetes or systemic inflammation.

One special phenotype is emphysema due to
alpha- 1-antitrypsin deficiency, appears early in life,
particularly in smokers and has a genetic base.
Garcia-aymerich J., Gomez FP. et.al. Thorax 2011:66:432-437
Videl R., Blanco I. et.al. Arch. Bronconeumol 2006:42:645-659
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
MeiLan K. Han., Agusti A. et.al. Am J. Respir Crit Care Med 2010;182:598-604
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Mixed COPD-Asthma Phenotype
 Patients present with characteristics of more than
one obstructive airway disease.
 About 13-20% COPD patients reported to have
overlap phenotypes.
 Increasing trend in elderly population –up to 50% in
those aged over 70 years.
 Marsh et.al have reported 55% COPD patients to be
mixed COPD- Asthma Phenotype.
Hardin M., Silverman E K et.al. Respri, Res. 2011.12:127.
Soriano J B., Davis K J. et.al. Chest. 2003:124:474:481.
Marsh S.E., Travers J. et.al Thorax 2008:63:761-767.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Definition of the Mixed (COPD-Asthma) Phenotype
 Recently consensus diagnostic criteria for Overlap (mixed)
phenotype has been defined by a group of experts.
 To be diagnosed with an Overlap phenotype a patient must
fulfil 2 Major criteria or 1 Major and 2 Minor criteria among
the following.
 A – Major criteria: very positive bronchodilator response (>
400ml and >15% FEV1), sputum eosinophilia or previous
diagnosis of asthma.
 B – Minor criteria: increased total serum IgE, previous
history of atopy or positive bronchodilator test (>200ml
and >12% in FEV1) on atleast 2 occasions.
Soler-Cataluna J.J., Coslo B. et.al. Consensus document on overlap asthma-COPD.
Phenotype. Arch Bronconeumol.2012.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Definition of the Mixed (COPD-Asthma) Phenotype
 The diagnosis of the mixed phenotype will be established
by the presence of a combination of the following factors:
 History of asthma and/or atopy,
 Reversibility in the bronchodilator test,
 Notable eosinophilia in respiratory and/or peripheral
secretions,
 High IgE,
 Positive prick test to pneumoallergens and
 High concentrations of exhaled NO
Papi A, Romagnoli M. et.al. Am J. Respir Crit Care Med. 2000:162:1773-1777.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Mixed (COPD-Asthma) Phenotype
Differential Treatment
 The clinical justification for the mixed phenotype lies in
its demonstrated sensitivity to the anti-inflammatory
action of Inhaled Corticosteroids.(ICS)
 Treatment with steroid reduces number of sputum
eosinophils.
 Serum Surfactant Protein –D (SP-D) levels indicate
rensponse to ICS.
 Greater airflow reversibility, a high concentration of
eosinophils in spontaneous or induced sputum or a
greater concentration of exhaled NO as markers of the
response to ICS in COPD, even in mild to moderate
stages.
Brightling CE., Monteiro W et.al. Lancet 2000:356:1480-1485, Brightling CE., Mckenna S. et.al.
Thorax 2005:60:193-198, Lee J.H., Lee Y.K. et.al. Resp. Med. 2010;104:542-549, Fujinoto K., Kubo K.
Chest 1999:115:697-702, Sin D.D., Man SFP et.al. Am J. Respir Crit Care Med. 2008;177:1207-1214.
ICS-Dr. S.N. Tripathy Oration.
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PHENOTYPES IN COPD
Mixed (COPD-Asthma) Phenotype
Differential Treatment
Based on the clinical, functional and inflammatory
characteristics of COPD patients. i.e. in Mixed phenotypes,
(instead of severity of airflow obstruction measured FEV1
alone), a high dose ICS treatment has been recommended.
The Canadian Guideline specify that “if the asthma
component in COPD is prominent, earlier introduction of
ICS may be justified”
The Japanese Guideline dedicates a chapter to “treatment
of COPD complicated by Asthma”.
The Spanish Guideline of COPD direct treatment according
to phenotypes.
Anderson D., MacNee W. Int. J. COPD.2009:4:321-335 Miravitlles M. Arch. Bronconeumol. 2009.45:27-34.
O’Donnel DE., Aaron S. et.al. Can. Respir. J. 2007;14(suppl B) 5-32. Nagi A., Aizawa H. et.al. 2009http/www/s.orjp.
Miravitlles M., Calle M., et.al. Arch. Bronconeumol. 2012:48:86-98.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Exacerbator Phenotype
 “Exacerbators” are defined as those COPD patients
who present with 2 or more exacerbations per year.
 These exacerbations should be separated by at least
4 weeks after the end of treatment of the previous
exacerbation or 6 weeks after the onset of the
exacerbation in cases that have received no
treatment.
 Exacerbator phenotype of COPD is independent of
disease severity.
 Estimation of Serum Amyloid-A (SAA) is a better
marker for diagonosis of exacerbations.
Soler-cataluna J.J., Rodriguez R.R. COPD 2010:7:276-284. Bozinovski S., Hutchinson A. et.al. Am J.
Respir Cirt Care Med. 2008:177:269-278. Shahab L., Jarvis M.J. et.al. Thorax 2006:61:1043-1047.
Seemungal T., Harper O.R. et.al. Am J. Respir Cirt Care Med.2001:164:1618-1623. Hurst J.R., Vestbo J.
et.al. N. Engl J. Med.2010:363:1128-1138.
ICS-Dr. S.N. Tripathy Oration.
 Hurst et al analyzed the frequency and associations of
exacerbation in 2138 patients enrolled in the Evaluation of COPD
Longitudinally to Identify Predictive Surrogate Endpoints
(ECLIPSE) study.
 Results
 Exacerbations became more frequent (and more severe) as the
severity of COPD increased.
 22% of patients with stage 2 disease, 33% with stage 3, and 47%
with stage 4 had frequent exacerbations.
 The single best predictor of exacerbations, across all GOLD
stages, was a history of exacerbations.
 phenotype was also associated with a history of gastroesophageal
reflux or heartburn, poorer quality of life, and elevated white-cell
count.
N Engl J Med 2010:363:1128-1138.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Exacerbator Phenotype
RISK FACTORS ASSOCIATED WITH REPEATED EXACERBATIONS.
Older age
COPD severity
Greater baseline dyspnea
Low FEV1
Low Pao2
History of previous exacerbations
Inflammation
Greater airway inflammation
Greater systemic inflammation
Bacterial load (stable phase)
Chronic bronchial hypersecretion
Comorbidity/extrapulmonary manifestations
Cardiovascular
Anxiety-depression
Myopathy
Reflux disease
M. Miravitlles., Moiriam C. et.al. Arch. Bronconeumo. 2012:48:86-98
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Exacerbator Phenotype
Differential Treatment
 Long-acting bronchodilators (LABA), have been
shown to reduce the frequency of exacerbations
 ICS in patients who present frequent exacerbations,
especially when associated with bronchodilators,
produces a significant reduction in the number of
exacerbations and an improvement in HRQL.
 Tiotropium has been shown to reduce exacerbation
rates, improve quality of life and increases FEV1.
Vogelmeier C., Hederer B. et.al. N. Engl. J. Med 2011:364:1093-1103. Kardos P., Wencker M
et.al. Am J. Respir Crit Care Med 2007:175:144-149. Wedzicha JA., Calverley PMA el.al. Am J.
Respir Crit Care Med 2008:177:19-26.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Exacerbator Phenotype
Differential Treatment
 Roflumilast is a new oral anti-inflammatory drug that
acts by selectively inhibiting phosphodiesterase IV
has been approved for preventing exacerbations in
patients with severe COPD with FEV1<50% with
cough and chronic expectoration and frequent
exacerbations.
 Roflumilast is indicated for the exacerbator
phenotype with chronic bronchitis.
 Macrolides may be administered for a prolonged
time, as they have anti-inflammatory and
immunomodulatory actions in addition to their
possible antibacterial action.
Calverley PMA., Sanchez-Toril F. et.al. Am J. Respir Crit Care Med 2007:176;154-161. Fabbri LM, Calverley
PMA. et.al. Lancet 2009:374:695-703. Sevilla-Sanchez D, Soy-Muner D. et.al. Arch.
Bronconeumol.2010:46:244-254.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Exacerbator Phenotype
Differential Treatment
 PULSE (Pulsed moxifloxacin Usage and its Long-term
impact on the reduction of Subsequent Exacerbation)
study, studied the efficacy of 5 days cycles of 400mg of
Moxifloxacin every 8 weeks in patients with stable
COPD.
 This treatment reduced the risk for exacerbation by
20% in the intention-to-treat (ITT) analysis, 25% in the
per-protocol (PP) analysis and 45% in patients who
presented purulent or mucopurulent sputum, without a
significant increase in bacterial resistances.
 Administration of Nebulized Tobramycin in Severe
COPD colonized by Pseudomonas aerugenosa reduced
No. of severe exacerbation by 42%.
Sethr S., Jones PW., et.al. Respir Res 2010:11:10. Dal Negro R., Micheletto C. et.al. Adv. Ther. 2008:25:10191030.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Definition of Emphysema-Hyperinflation Phenotype
COPD patients who present dypnoea and intolerance
to exercise as the predominating symptoms.
They are characterized by presence of
functional data of hyperinflation, Emphysema on
HRCT study, variability of the Carbon Monoxide (CO)
diffusing capacity(DLCO), tendency towards a lower
BMI.
Miravitlles M. et.al. Arch Bronconeumol 2012:48:86-98.
Grydeland TB., Thorsen et.al. Respir Med. 2011;105:343-351.
Mair G. Maclay J. et.al. Respir Med 2010:104:1683-1690.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Diagnosis of Emphysema-Hyperinflation Phenotype
 HRCT.
 FEV1 is strongly related to COPD severity.
 FEV1% Predicted is weakly related to the extent of
emphysema.
 Reduction in DLCO is more strongly correlated with
the severity of emphysema as assessed by HRCT.
Hoidal JR., Eur Respir J. 2001 18:741-743,
Baldi S. Miniati M. et.al. Am. J. Respir Crit Care Med 2001:164:585-589.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Differential Treatment of EmphysemaHyperinflation Phenotype
 Several studies have demonstrated improvements in
forced vital capacity (FVC) after administration of
long
acting
bronchodilator
(LABA),
with
improvement in Inspiratory Capacity and reduction
in air trapping with no significant improvements in
FEV1.
 This improvement in the volume (FVC) without
changes in airflow(FEV1) is more frequent as the
bronchial obstruction becomes more severe.
Newton MF., O’Donnell DE et.al. Chest 2002:121:1042-1050,
Tashkin DP, Celli B et.al. Am J. Respir Crit Care Med 2008:177:164-169.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Differential Treatment of EmphysemaHyperinflation Phenotype
 NETT study also did not demonstrate the superiority
of surgical intervention versus conservative
treatment, however, in patients with emphysema in
the upper lobes and low exercise capacity, a
significant reduction in mortality was achieved after
lung volume reduction surgery (LVRS).
 In addition, the improvement in lung function after
surgery was accompanied by a significant reduction
in the number of exacerbations and prolonged
period of exacerbation-free life.
Martinez FJ., Foster G. et.al. Am J. Respir Crit Care Med 2006:173:1326-1334.
Washko GR., Fan VS et.al. Am J. Respir Crit Care Med 2008:177:164-169.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Differential Treatment of EmphysemaHyperinflation Phenotype
 Long-acting bronchodilators (LABA) are the
Principal drug for treatment.
 They improve symptoms and exercise capacity and,
consequently, improve the state of health
 Benefits reached at the clinical level do not translate
into an improvement of the degree of obstruction
(changes in FEV1) with improvements in degree of
dyspnea and exercise tolerance.
 Tiotropium has been shown to improve quality of
life and degree of dyspnoea.
Tashkin DP., Cooper CB. Chest 2004:125:249-259.
O’Donnell FT., Gerken F. et.al. Eur Respir J. 2004:23:832-840
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Differential Treatment of EmphysemaHyperinflation Phenotype
 Anti-inflammatory treatment with inhaled
corticosteroids(ICS), has not been shown to be as
effective as in other phenotypes.
 Oral anti-inflammatory Roflumilast did not offer good
results for reduction of exacerbations.
Lee JH., Lee YK et.al. Respir Med 2010:104:542-549.
Rennard SI., Calverley PMA. et.al. Respir Res 2011:12-18.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
Differential Treatment of EmphysemaHyperinflation Phenotype
 Patients
with
an
emphysema-hyperinflation
phenotype could benefit more from a double
bronchodilator therapy -- Formoterol and Tiotropium,
Fluticasone-Salmeterol combination.
 They are benefitted more from respiratory
rehabilitation due to its beneficial effects on dyspnea
and exercise tolerance.
Rabe KF., Timmer W. et.al. Chest 2008:134:255-262,
Casaburi R, Zuwallack R.N. Eng. J. Med 2009:360:1329-1335.
ICS-Dr. S.N. Tripathy Oration.
PHENOTYPES IN COPD
SUMMARY
COPD is a leading cause of morbidity and mortality Globally.
 It is on the rise.
FEV1 can not be used in isolation for optimal diagnosis,
assessment of severity, follow-up and response to therapy.
Significant heterogeneity of clinical presentation, disease
progression and response to different medications exists.
Phenotypes should be able to classify COPD patients into
subgroups for determining the specific therapy to achieve
better clinical results.
Phenotyping in COPD is a relatively young endeavor.
Efforts should be made to bring out International consensus
statement on phenotypes based management of CPOD.
ICS-Dr. S.N. Tripathy Oration.