Chronic Obstructive Pulmonary Disease

Updated Guidelines and Newer Therapies

Heba Ismail, MD
Assistant clinical Professor
Division of Pulmonary and Critical Care Medicine
University of California, Irvine Medical Center
E-mail, ismailh@uci.edu
Disclosure
None
Definition
The international Global initiative on Chronic
Obstructive Lung Disease (GOLD), (WHO/NIH
2009) defines COPD as:

A preventable and treatable disease with some

significant extra-pulmonary effects that may
contribute to the severity in individual patients.

The pulmonary component is characterized by

airflow limitation that is not fully reversible.

The airflow limitation is usually progressive and

associated with an abnormal inflammatory response
of the lung to noxious particles or gases.
Definition
This definition no longer describes emphysema, or
chronic bronchitis.
COPD is much more a small airways (< 2 mm) disease, pathologically a chronic
bronchiolitis caused predominantly by prolonged exposure to tobacco smoke.

Destructive alveolar wall rupture occurs from an

imbalance between elastases and anti-elastases, and
prolonged activation of inflammatory cells causing
regional elastin damage with alveolar emphysema.

Loss of lung elastic recoil is the key pathophysiological

finding, and occurs with emphysema perhaps before loss
of alveolar wall and surface area measurable by carbon
monoxide diffusing capacity (DLco).
COPD and Chronic Bronchitis
Chronic bronchitis per se is a smoking related disease of large
airways that often resolves after smoking cessation.

Patients with COPD who suffer from chronic bronchitis generally

show:
Faster functional decline
More exacerbations
Greater morbidity and mortality

A greater percentage of smokers with chronic cough can have

COPD as compared with smokers without symptoms when
functionally reassessed after 8 years.

Chronic bronchitis can be considered as both a risk factor for

COPD, and a worse prognostic factor in the presence of COPD.
Pathology
Pathological changes of COPD are found in:
Airways
Lung Parenchyma
Pulmonary Vasculature

Pathological changes include:

Chronic Inflammation
Structural changes
Pathogenesis
Pathogenesis
Oxidative Stress
Protease-Antiprotease Imbalance
Inflammatory cells
Inflammatory Mediators
Pathophysiology
Pathologically, COPD is characterized by two
distinct and frequently coexisting aspects:

Small airway abnormalities --- will contribute to

airflow limitation by narrowing and obliterating the
lumen and by actively constricting the airways,
therefore increasing the resistance---decreased FEV1

Parenchymal destruction (or emphysema)--- airflow

limitation and decreased gas transfer
Pathophysiology
Collapse of small airways during expiration lead to
further static hyperinflation.

These early changes are not detectable by simple

pulmonary function tests (PFT)

Reliance on the FEV1/FVC < 0.70 and FEV1 % of

predicted remains the current state of the art in COPD
screening and staging.

A normal DLco does not rule out COPD.

Pathophysiology
Airflow limitation and Air Trapping

Gas Exchange Abnormalities

Mucus Hypersecretion

Pulmonary Hypertension

Systemic Features
COPD
No blood test, imaging study, or lung function can
completely describe impairment from COPD.

The BODE Index is a valuable tool

Predicting survival in clinical research
Assessing disease burden and impairment utilizing

Body mass index (BMI)

FEV1 expressed as % of predicted
Severity of dyspnea (the cardinal symptom of COPD)
Exercise capacity or 6-minute walk distance (6MWD)
Epidemiology
The prevalence of COPD varies by country
It is generally linked to the prevalence of tobacco smoking
There is also a link to air pollution from the burning of wood and other biomass
fuels

Worldwide, COPD is one of the leading cause of morbidity and

mortality

COPD is the 4th leading cause of mortality in the USA, and is also
the only one of the top five leading causes of death that is
continuing to rise, doubling from 1970 to 2002

It is projected that COPD will become the third leading cause of

death worldwide by 2020

COPD deaths among women in the USA have been rapidly rising
since the 1970s and have exceeded male COPD deaths since 2000
Epidemiology
COPD presents an increasing social and economic burden.

COPD patients incur health care costs associated with

frequent clinic visits, urgent care visits, and hospitalizations.

Home medical therapies, including oxygen therapy, visiting

nursing services, and rehabilitation add to the cost .

The health-care expenditure for each COPD patient cost on

average $6,000 annually.

In 2002, the estimated USA direct medical cost of COPD

was $18 billion while indirect costs including lost wages and
decreased productivity were estimated at $14.1 billion.
COPD phenotypes
Asthma-COPD overlap syndrome
Exacerbators
Emphysema-Hyperinflation

Chronic Bronchitis can accompany any of the three

phenotypes
Proportional Venn diagram presenting the different phenotypes within the Wellington Respiratory Survey study population. The large
black rectangle represents the full study group. The clear circles within each coloured area represent the proportion of subjects with
COPD (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7). The isolated clear circle represents
subjects with COPD who did not have an additional defined phenotype of asthma, chronic bronchitis or emphysema. (Reproduced with
permission from Marsh SE, Travers J, Weatherall M et al. Proportional classifications of COPD phenotypes. Thorax 2008; 63: 761-767.)
COPD Classification
GOLD has classified COPD into four
stages based on spirometric values and
thus on severity of airflow obstruction
(Table 1) .
Table 1
Classification of COPD
COPD, Management
The focus of COPD treatment should be
Relief of symptoms
Improving exercise tolerance and overall health status
Prevention and timely treatment of exacerbations
Preventing disease progression
Reducing mortality .
COPD Management
Non pharmacotherapy
Pharmacotherapy
Surgery
Minimally Invasive Surgery
Smoking Cessation

The Global Initiative for Chronic

Obstructive Lung Disease (GOLD)
guidelines emphasize that smoking
cessation is, the single most effective and
cost-effective way to reduce exposure to
COPD risk factors.
Pulmonary Rehabilitation
According to the ATS statement on pulmonary rehabilitation,
it is defined as a
Multidisciplinary program of care for patients with chronic
respiratory impairment that is individually tailored and designed
to optimize physical and social performance and autonomy
Pulmonary rehabilitation improves quality of life, by improving
exercise tolerance, and dyspnea.
Pulmonary rehabilitation was found to increase peak workload
by 18%, and peak oxygen consumption by 11%.

Pulmonary rehabilitation should be considered for COPD

patients with reduced exercise tolerance and limitation of
their daily activities secondary to their disease.
COPD, Pharmacotherapy
Pharmacologic therapy is able to significantly
improve the quality of life and reduce the
frequency of exacerbations

BUT
Unable to halt the annual decline in FEV1 or
unequivocally reduce mortality, with the
important exception of oxygen therapy where
indicated.
Oxygen Therapy
Long-term oxygen therapy (more than 15 hours
a day) has been shown to
Improve survival
Exercise tolerance
Pulmonary hemodynamics including pulmonary artery pressure,
lung mechanics and mental status.
Indications of long term oxygen therapy include:
PaO2 at or below 55 mmHg or/ SaO2 of less than or equal to
88%
PaO2 between 55 mmHg and 60 mmHg, SaO2 of 89% if there is
evidence of pulmonary hypertension, peripheral edema
suggesting congestive heart failure or polycythemia.
Pharmacotherapy
Bronchodilators
They do not alter the decline in lung function.
They decrease expiratory trapped air volume
and reduce dynamic hyperinflation during
exercise as well as at rest.
They are prescribed in both short- and long-
acting forms for immediate (rescue) and
sustained relief, respectively.
Pharmacotherapy
Long-acting bronchodilators are recommended for
patients with moderate to severe COPD.

In the largest trial of a Salmeterol, long-acting beta-2

agonist (LABA), Toward a Revolution in COPD Health
(TORCH), patients with a mean forced expiratory
volume in one second (FEV1) of 44% of predicted were
randomly assigned to one of four treatment arms for 3
years:
Salmeterol alone (50 mcg twice daily)
Fluticasone alone (500 mcg twice daily)
Combination of both
Placebo
Pharmacotherapy
The Salmeterol alone and combination arms each
revealed improved lung function, health-related
quality of life, and reduced exacerbation rates
compared to the placebo arm.

No statistically significant mortality reduction was

seen.

However, the combination of Fluticasone and

Salmeterol showed a trend towards a significant
reduction of all-cause mortality by 17.5% in 3
years compared to placebo.
 TORCH

Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease
Peter M.A. Calverley, M.D., Julie A. Anderson, M.A., Bartolome Celli, M.D., Gary T. Ferguson, M.D., Christine Jenkins, M.D., Paul W. Jones, M.D., Julie C. Yates, B.S., and Jrgen
Vestbo, M.D. for the TORCH investigators
N Engl J Med 2007; 356:775-789February 22, 2007DOI: 10.1056/NEJMoa06307
Pharmacotherapy
Tiotropium, was assessed in a randomized trial Understanding Potential
Long-Term Impacts on Function with Tiotropium (UPLIFT).

Among patients with moderate (45%) and severe (44%) COPD, Tiotropium
or placebo was added to ongoing care, that is, inhaled corticosteroids,
long-acting beta-2 agonists, and/or theophylline, for a duration of 4 years.

Tiotropium significantly reduced the risk of exacerbations and associated

hospitalizations and respiratory failure when added to usual care.

There was no difference in the annual rate of decline of FEV1 or mortality

between the two groups .

An intention-to-treat analysis that assessed mortality after 4 years, the use

of Tiotropium reduced all cause mortality by 13% (HR = 0.87, 95% CI
0.760.99, ).
Pharmacotherapy
The combination of bronchodilators of different classes and
durations may provide an improved effect with fewer side effects .

For example, the combination of a LABA and an anticholinergic

(Tiotropium) showed an improved FEV1 by the end of a 12-week
trial .

In another study, the use of a short acting beta-agonist plus an

anticholinergic showed a greater and longer-lasting FEV1
improvement when compared to each drug alone .

No clear data are available as to which long-acting bronchodilator

combination provides the best relief.

Current guidelines recommend weighing the risks and benefits of

each for the individual patient .
Pharmacotherapy
Although pulmonary inflammation plays an important
role in the pathophysiology of the disease, inhaled
corticosteroids (ICS) have not definitively been shown
to decrease the rate of lung function decline or change
COPD morbidity per se.

However, the addition of an ICS may prove beneficial for

some patients.
Pharmacotherapy
In the TORCH study, the combination of a LABA
plus ICS resulted in a decrease in the number of
exacerbations along with sustained benefits in
health status and sustained improvement in FEV1
when compared to Placebo, Salmeterol alone and
Fluticasone alone .

This combination is typically reserved for patients

with GOLD stages 3 and 4 with recurrent
exacerbations, or for those who have baseline
eosinophilic component of their disease or
associated asthma.
Pharmacotherapy
A recent meta-analysis readdressed the possibility of a
favorable effect on mortality when combining ICS and
bronchodilators in COPD.

Use of an ICS combined with LABA demonstrated a 20%

reduction in total mortality, with a mortality risk ratio of
0.80 (95% CI, 0.690.94).

However, use of a LABA or Tiotropium alone did not

decrease the mortality rate .

There is also concern that the use of high dose ICS in

patients with COPD may be associated with an increased
risk of pneumonia.
 Therapy at Each Stage of COPD
I: Mild II: Moderate III: Severe IV: Very Severe

FEV1/FVC < 70%

FEV1 < 30%

predicted
FEV1/FVC < 70% FEV1/FVC < 70% or FEV < 50%
1
predicted plus
FEV1/FVC < 70% 50% < FEV1 < 30% < FEV1 < chronic
80% 50% predicted respiratory failure
FEV1 > 80% predicted
predicted
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Add regular treatment with one or more long-acting
bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if
repeated exacerbations
Add long term
oxygen if chronic
respiratory failure.
Consider surgical
treatments
Novel Pharmacotherapy
Phosphodiesterase (PDE) Inhibitors
N-Acetylcysteine (NAC)
TNF Inhibitors-Infliximab
ABX-IL8
Anti-leukotriene Drugs
Prophylactic Use of Macrolides
Vitamin D
Novel Pharmacotherapy
Inflammatory cells such as neutrophils, CD8 lymphocytes, and
macrophages, express predominantly phosphodiesterase (PDE)
type 4.

PDE type 4 hydrolyzes cyclic adenosine monophosphate (cAMP) in

inflammatory cells.

By inhibiting PDE type 4, intracellular cAMP concentrations

increase which leads to activation of protein kinase A,
phosphorylation and inactivation of target transcription factors,
which ultimately result in reduction of cellular inflammatory
activity.

While theophylline is a nonspecific PDE inhibitor (thus with a large

side-effect profile including diarrhea, seizures and cardiac
arrhythmias), several new drugs have been tested that target PDE
type 4 specifically, notably Cilomilast and Roflumilast
PDE-4
PDE-4 Inhibitors
The safety and efficacy of Cilomilast (15 mg twice daily)
was evaluated in
A double-blind placebo-controlled study
Significant increase in FEV1 as well as fewer exacerbations over a 24-
week period.

Gastrointestinal side effects (nausea and diarrhea) were greater in

the first 3 weeks of the study in the treatment arm.

Cilomilast has been evaluated in three additional multicenter,

randomized, placebo-controlled phase III trials.
The change of FEV1 (from 3040 mL) compared to placebo was significant in
only two of the four studies.

Overall, these studies did not show as large of improvements in

FEV1 as was expected based on phase II trials.
PDE-4 Inhibitors
Roflumilast is a more potent PDE type 4 inhibitor compared to
Cilomilast .

In a phase III multicenter placebo-controlled trial, 1411 patients

were randomly assigned to receive Roflumilast 250 mcg, Roflumilast
500 mcg, or placebo daily for 24 weeks.

Post-bronchodilator FEV1 at the end of treatment significantly

improved for both groups of Roflumilast when compared to
placebo (74 mL with the lower dose and 97 mL with the higher
dose medication).

Both groups suffered fewer mild exacerbations while moderate to

severe exacerbations were unchanged.

The most common side effects were also diarrhea and nausea.
PDE-4 Inhibitors
Two randomized clinical trials on the use of Roflumilast
compared to placebo were published in 2009.

Patients in these studies had COPD with severe airflow

obstruction, documented cough and sputum production,
and a history of frequent COPD exacerbations in the
past year.

In pooled analysis, the pre-bronchodilator FEV1

increased by 48 mL among those with the treatment
drug, a statistically significant improvement compared to
placebo.
PDE-4 Inhibitors
Moderate to severe exacerbations were also
significantly less in the treatment arm.

When compared to placebo, the addition of

Roflumilast to Salmeterol was associated with a
49 mL prebronchodilator FEV1 increase, and an
80 mL increase when added to Tiotropium

Side effects such as nausea, diarrhea and weight

loss contributed to greater patient withdrawal
Surgery and Minimally Invasive
(Non-Surgical) Approaches
Bullectomy
Lung Volume Reduction Surgery
Minimally Invasive approaches
Endobronchial Blockers
Bronchial Fenestration and Airways Bypass
Endobronchial Valves
Biological Lung Volume Reduction (Sealants)
Surgery for COPD
Bullectomy
Bullectomy appears to be of benefit in highly selected
patients resulting in short-term improvements in airflow
obstruction, lung volumes, hypoxaemia and hypercapnia,
exercise capacity, dyspnea, and health-related quality of life.

Surgical mortality ranges from 0-22.5%

Long-term follow-up data are more limited with 1/3-1/2 of

patients maintaining benefits for ~5 yrs

Patient selection
most investigators have attempted to identify optimal surgical
candidates on the basis of pulmonary function and radiographic
features
Bullectomy
Patient Selection
Lung Volume Reduction Surgery
LVRS
LVRS, NETT
Methods
A total of 1218 patients
with severe emphysema
underwent pulmonary
rehabilitation and were
randomly assigned to
undergo lung-volume
reduction surgery or to
receive continued medical
treatment
LVRS, NETT
LVRS, NETT
Results
Overall mortality was 0.11 death per person-year in both treatment
groups.

After 24 months, exercise capacity had improved by more than 10 W in

15 percent of the patients in the surgery group, as compared with 3
percent of patients in the medical-therapy group (P<0.001).

With the exclusion of a subgroup of 140 patients at high risk for death
from surgery according to an interim analysis, overall mortality in the
surgery group was 0.09 death per person-year, as compared with 0.10
death per person-year in the medical-therapy group (risk ratio, 0.89;
P=0.31).

Exercise capacity after 24 months had improved by more than 10 W in

16 percent of patients in the surgery group, as compared with 3 percent
of patients in the medical-therapy group (P<0.001).
LVRS, NETT
Among patients with predominantly upper-lobe
emphysema and low exercise capacity, mortality was
lower in the surgery group than in the medical-
therapy group (risk ratio for death, 0.47; P=0.005).

Among patients with nonupper-lobe emphysema and

high exercise capacity, mortality was higher in the
surgery group than in the medical-therapy group (risk
ratio, 2.06; P=0.02).
LVRS, NETT
Conclusions
Overall, lung-volumereduction surgery
Increases the chance of improved exercise
It does yield a survival advantage for patients with both
predominantly upper-lobe emphysema and low base-line
exercise capacity.
Patients previously reported to be at high risk and those
with nonupper-lobe emphysema and high base-line
exercise capacity are poor candidates for lung-volume
reduction surgery, because of increased mortality and
negligible functional gain.
LVRS
Patient Selection
A systematic review proposed the
following features, as determined by
expert opinion, to be associated with
better outcomes:
Smoking-related emphysema
Heterogeneous emphysema with surgically
accessible "target" areas
Bilateral surgery
Good general fitness/condition and thoracic
hyperinflation
LVRS
Patient Selection
Endo-bronchial Valves
Endo-bronchial valves (EBV) are one-way
valves that prevent air from entering the
airway distally but allow for ventilation of the
expired gas and drainage of distal secretions.

Two-valve designs have been studied in

separate multicenter reports (Zephyr EBV,
Pulmonx Corp and IBV, Spiration, Inc.).
The Zephyr EBV
The Zephyr EBV, formerly known as Emphasys EBV,
consists of a stent-like self-expanding retainer made
of nitinol, which is wrapped in molded silicone.

In the center of the retainer is a duckbill one-way

valve that allows outflow of gas and secretions during
exhalation but does not permit air entry during
inhalation.

The EBV is compressed via a loader system, placed

onto a delivery catheter, and a guide-wire directs this
catheter to the targeted area, all via the working
channel of a bronchoscope.
The Zephyr EBV
N Engl J Med 2010; 363:1233-1244September 23, 2010DOI: 10.1056/NEJMoa090092
Zephyr EBV, VENT
The EBV valve was tested in The Endo-bronchial
Valve for Emphysema Palliation Trial (VENT).

A multicenter, randomized controlled trial of 321

subjects with severe heterogeneous emphysema
(220 treated with Zephyr EBV and 101 treated as
controls).

At 6-month follow-up, the treatment group had

statistically significant improvements in the
primary endpoints of FEV1
(+6.8%,P=.002 ) and 6MWT (+5.8%,P=.019 ).
Zephyr EBV, VENT
There were also significant improvements in
secondary outcomes of St. Georges
Respiratory Questionnaire (SGRQ) and
BODE index compared with control.

The 6-month mortality was 2.8% among the

treatment group (zero in the control group),
and cumulative mortality rate over 1-year
follow-up was 3.7% for the Zephyr group
and 3.5% for the control group (P=1.000).
Zephyr EBV, VENT
Complications related to the device were
Valve migration
Pneumonia distal to the valve
Granulation tissue

In final review of various outcomes from this

trial
The FDA advisory panel recommended
against approval of this device, citing that
the benefits were not large enough to
overcome the risks.
IBV, Spiration
The Intrabronchial Valve (IBV;
Spiration) is also made of nitinol
and has 5 distal anchors and 6
proximal support struts that are
covered by a synthetic
polyurethane polymer

These struts expand to form an

umbrella shape to allow for
sealed placement in the airway.

Air and mucus are able to flow

around the edges of the
membrane. The valve has two
delivery system options via a
loading device through the
working channel of a flexible
bronchoscope.
Spiration IBV
The largest trial reported
An open-label study.
A total of 98 patients were enrolled at 13 international
centers over a 3-year period with the intent of bilateral
treatment of upper lobe predominant emphysema.
Bilateral treatment was done in 95 of the 98 patients,
and a total of 659 valves were placed.
While they did not find statistically significant
improvements in spirometry and lung volume
measurements at 3 and 6 month follow-up, the patients
SGRQ decreased by greater than 4 (a 56%
improvement) at 6 months.
Spiration IBV
There were a total of 8 pneumothoraces, one of which was a
tension pneumothorax that occurred on post-procedure day
4 and resulted in the death of the patient.

There were no episodes of valve migration or expectoration.

The most common post-procedure adverse event was

bronchospasm, which resolved after one bronchodilator
treatment in 3 cases but required several repeated
treatments in 2 other patients.

In the latter two cases, the bronchospasm lasted for 24 to 48

hours, resolved after valve removal, and was assumed to be
related to the valves.
 Current status of bronchoscopic lung
volume reduction with endo-bronchial
valve

Methods
Searches for appropriate studies were undertaken on
PubMed and Clinical Trials Databases using the search
terms COPD, emphysema, lung volume reduction and
endobronchial valves

Thorax. 2014 Mar;69(3):280-6. doi: 10.1136/thoraxjnl-2013-203743. Epub 2013 Sep 5. Current status of
bronchoscopic lung volume reduction with endobronchial valves. Shah PL1, Herth FJ.
 Current status of bronchoscopic lung
volume reduction with endo-bronchial
valve
Results
The evidence from the randomized clinical trials suggests that complete
lobar occlusion in the absence of collateral ventilation or where there is
an intact lobar fissure are the key predictors for clinical success.

Other indicators are greater heterogeneity in disease distribution

between upper and lower lobes

The proportion of patients that respond to treatment

improves from 20% in the unselected population to 75% with
appropriate patient selection

The safety profile for endobronchial valves in this severely affected

group of patients with emphysema was acceptable and the main adverse
events observed were an excess of pneumothoraces.

Thorax. 2014 Mar;69(3):280-6. doi: 10.1136/thoraxjnl-2013-203743. Epub 2013 Sep 5. Current status of bronchoscopic
lung volume reduction with endobronchial valves. Shah PL1, Herth FJ.
 Current status of bronchoscopic lung
volume reduction with endo-bronchial
valve

Conclusion

Selected patients have the potential of significant benefit in terms

of lung function, exercise capacity and possibly even survival

These considerations are essential in-order to maximize patient

benefit in a resource-limited environment and also to ensure
that beneficial treatments are available for the appropriate
patient

Thorax. 2014 Mar;69(3):280-6. doi: 10.1136/thoraxjnl-2013-203743. Epub 2013 Sep 5. Current status of bronchoscopic lung volume reduction with
endobronchial valves. Shah PL1, Herth FJ.
 This article describes first experiences in a patient with five
endobronchial valves in the right upper lobe who needed urgent
surgery due to lumbar disc herniation with neurological
impairment.

The use of broncho-dilating volatile anesthetics and adjusting the

ventilatory settings with long expiration times and low peak
pressure in a pressure controlled mode seems favorable in these
patients.

In conclusion the care of patients with implanted endobronchial

valves after ELVR does not differ from COPD patients without
ELVR.
COPD
Assessment of General operative risk
Methodologies of
Assessment
Essential components of
the preoperative
assessment are a
careful history
physical examination
assessment of the
functional capacity
Close attention should be
paid to a history of smoking,
dyspnea, cough and sputum
production.
Functional capacity can be
assessed by the ASA
questionnaire
COPD
Assessment of General Operative Risk
The perioperative risk of venous thromboembolism and potential
prophylactic strategies should be assessed for all patients.

In patients with a known diagnosis of COPD, or those at increased

risk for COPD, preoperative spirometry should be performed.
Identification of severe airflow obstruction may be particularly
important in patients who are candidates for upper abdominal or
thoracic surgical procedures

Analysis of arterial blood gas (ABG) composition should be

available for patients with moderate-to-severe COPD.

Since patients with COPD are at increased risk of pulmonary

neoplasm and other pathologies, a preoperative chest radiography,
if not recently performed, is reasonable
Surgery in the COPD Patient
Ophthalmologic procedures
low mortality rate (<1%)
cough may be of concern because of increased ocular pressure.
excessive suppression of cough may lead to retained secretions, atelectasis, pneumonitis and problems
in gas exchange.
Topical, ophthalmologic, -blocker medications, used to reduce intraocular pressure, may
precipitate bronchospasm and cardiorespiratory failure

Head/neck procedures
Procedures involving the airway carry an increased risk of postoperative pneumonia
Management of secretions in the patient who has undergone laryngectomy may require
early postoperative humidification.

Orthopaedic procedures
Orthopedic procedures are associated with a relatively high frequency of venous
thromboembolism
In the patient with COPD, pulmonary embolism is associated with greater mortality

Lower abdominal/pelvic surgery

In general, COPD does not increase the risk of perioperative risk with lower abdominal
procedures.
Surgery in COPD Patient
Upper abdominal surgery
Patients who undergo surgery in the upper abdomen are at risk for perioperative
pulmonary complications
COPD independently increases this risk
Complications are particularly liable to occur in persons with predisposing factors
such as morbid obesity, cigarette smoking, heart disease and advanced age

Cardiovascular surgery
COPD is a common cause of perioperative pulmonary dysfunction in patients
undergoing cardiac surgery
Screening for COPD in this patient population is particularly important because
COPD has been associated with prolonged intubation after cardiac surgery

Abdominal vascular surgery

Patients who undergo elective major abdominal vascular surgery are at high risk of
postoperative pulmonary complications
Patients with COPD are at particularly high risk
Factors associated with the need for prolonged mechanical ventilation include a
history of heavy cigarette smoking, preoperative arterial hypoxaemia and major
intraoperative blood loss
Surgery in COPD patient
Lung surgery
Preoperative pulmonary function studies have a well-
documented role in the evaluation of patients who are
to undergo lung surgery
Procedure-related issues
Thoracotomy has a reversible (several months)
adverse effect on lung function
Lung resection
Lobectomy results in an additional ?10% reduction
in forced vital capacity (FVC) at 6 months after
surgery
Pneumonectomy usually causes a permanent
reduction of about 30% in all lung function. This
decrement in lung function can prove devastating to
COPD patients
COPD and Lung Resection
Patients with preserved lung function should tolerate resection well in the
absence of other comorbid conditions.

Preoperative values of forced expiratory volume in one second (FEV1) >2

L (or >80 percent predicted) and DLCO >80 percent predicted suggest
that the patient should be able to tolerate surgery including
pneumonectomy.

For patients with preoperative FEV1 <2 L (or <80 percent predicted) or
DLCO <80 percent predicted, the predicted postoperative (PPO) FEV1
and DLCO should be calculated, based upon the preoperative values and
the fractional functional contribution of the lung to be resected.
PPO FEV1 = preoperative FEV1 x (1 y/z)
where y = number of functional or unobstructed lung segments to
be removed, and z = total number of functional segments (typically
19)
COPD and Lung Resection
Cardiopulmonary exercise testing (CPET) is useful when the results of PPO
FEV1, PPO DLCO, and/or low technology exercise testing do not clearly define
the patients risk as either high or low.

Patients who can achieve a VO2 max >20 mL/kg per minute are likely to have
an acceptable rate of postoperative complications, whereas those with a value
<10 mL/kg per min (or less than 35 percent predicted) are probably best
managed by nonsurgical modalities.

For those with VO2 max values in between 10 and 20 mL/kg per minute, the
predicted postoperative (PPO) VO2 max is calculated. If the PPO VO2 max is
<10 mL/kg per min or <35 percent, surgical candidacy is poor and
nonresectional options should be sought. On the other hand, if the PPO VO2
max is 10 mL/kg per min or 35 percent, resection is not absolutely
contraindicated, but the patient must understand the higher risk if either the
PPO FEV1 or DLCO is <30 percent predicted.
Peri-operative Management
General factors include the following.
Every effort should be made to aid with smoking cessation Smoking
cessation at least 4-8 weeks preoperatively is optimal.
Optimization of lung function using inhaled bronchodilators (in
patients with severe COPD can decrease postoperative
complications.
Oral Corticosteroids.

Pulmonary rehabilitation should be

considered in high-risk patients undergoing
elective procedures.
Pre- and postoperative pulmonary rehabilitation have been shown
to decrease postoperative pulmonary complications after abdominal
surgery
Intra-operative Management
The COPD patient may be more sensitive to the ventilatory
depressant effects of the analgesic, regional and general anaesthetic
agents used .

Volatile anesthetics, intravenous anaesthetics and neuromuscular

blocking agents vary in their ability to provoke unwanted
autonomic effects and alter airway reactivity .

The risk of pulmonary complications may be higher with the use of

the long-acting neuromuscular blocker pancuronium than shorter-
acting atracurium or vecuronium
Intraoperative Management
The role of general versus regional anaesthesia remains
controversial.

A meta-analysis suggested that neuroaxial blockade with

epidural or spinal anaesthesia decrease postoperative
mortality, deep venous thrombosis, pulmonary embolism,
transfusion requirements, pneumonia and respiratory
depression

A subsequent randomized trial of intraoperative and

postoperative epidural analgesia plus general anaesthesia for
upper abdominal surgery in high-risk patients (7-8% with
severe COPD) noted only a reduction in postoperative
respiratory failure (number needed to treat to prevent one
episode of respiratory failure was 15).
Intraoperative Management
In COPD patients, the combination of thoracic epidural
and general anesthesia may result in less shunting and
better oxygenation during thoracic surgical procedures.

Thoracic epidural anaesthesia appears to have only

limited deleterious effects on pulmonary function in
patients with severe COPD and has been used as the
primary mode of anaesthesia for COPD patients
undergoing chest wall surgery .

The immediate postoperative recovery period is a

period of high risk because of the possibilities of
respiratory muscle dysfunction, acidemia, hypoxaemia
and hypoventilation.
Postoperative Management
Early mobilization, deep breathing, intermittent positive-pressure breathing
or incentive spirometry have been reported to decrease postoperative
complications after upper abdominal surgery.

A necessary component of postoperative management is effective

analgesia.
Epidural administration may offer superior analgesia with less sedation by promoting patient
mobility and deep breathing .

Indications for postoperative mechanical ventilation are respiratory failure

with retained secretions, atelectasis and pneumonia.

Continuation of preoperatively prescribed respiratory medications is

standard therapy.
Postoperative Management
Weaning from mechanical ventilation patients with COPD
who have had cardiac surgery may be prolonged

The patient should be ventilated at a level that maintains

arterial carbon dioxide tension at the preoperative level with
a normal pH.

In the COPD patient who is difficult to extubate, gradual weaning

may permit the patients cardiovascular status to become
sufficiently stable to tolerate assumption of the full work of
breathing
Thank you
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COPD and Pulmonary Hypertension
One of the well-known complications of COPD is
pulmonary hypertension (PH).

Pulmonary Hypertension is defined as

Mean pulmonary artery pressure (PAP) of > 20mmHg at rest,
which is different from the standard definition of pulmonary
arterial hypertension (PAH) defined as a mean PAP>25mmHg.
However in some recent studies, PH secondary to COPD was
defined using the latter standard.

The exact prevalence of pulmonary hypertension resulting

from COPD remains unknown.

A few studies based on hospitalized patients have estimated

the prevalence of PH secondary to COPD as defined by a
mean PAP >20 mmHg to range between 35% and 90%.
COPD and Pulmonary Hypertension
The mechanisms of development of PH in COPD patients include
increase in pulmonary vascular resistance secondary to alveolar hypoxia
increase in pulmonary capillary wedge pressure during exercise in
patients with severe emphysema and hyperinflation.

PH in COPD patients can be divided into two main features,

The first one occurring at rest in the setting of stable COPD. The
majority of these patients will have a mild degree of PH with an average
mean PAP of 25 to 30 mmHg. However if the mean PAP is >40 mmHg,
it is usually associated with cardiopulmonary disease, acute
exacerbation, or disproportionate PH which will be discussed
separately.

The second feature includes worsening of PH during exercise, sleep or

COPD exacerbation.
COPD and Pulmonary Hypertension
Worsening of PH with a marked increase in mean PAP is noted in
patients with advanced COPD and PH at rest.

In these patients, a mean PAP of 25 mmHg during rest may

increase to 50 to 60 mmHg during 30 to 40 watt exercise, sleep or
acute COPD exacerbations, which lead to symptoms of dyspnea on
even daily activities like climbing or walking
COPD and Pulmonary Hypertension
Right heart catheterization (RHC) remains the gold standard
for diagnosis of PH in these patients

RHC can be performed at rest, during steady-state exercise,

and after therapeutic interventions (vasodilators)

There are no clear guidelines regarding indications of

treatment of PH in COPD patients

The necessity of treatment of mild or moderate PH in these

patients remain questionable, however some may argue that
acute increase in PAP with worsening of PH during acute
COPD exacerbations and/or exercise may contribute to
development of right-sided heart failure.
COPD and Pulmonary Hypertension
Prior to initiation of treatment, all patients must have
RHC to evaluate PH severity and to rule out other
explanations for dyspnea such as left sided heart failure.

Treatment may include oxygen therapy and pulmonary

vasodilators.

Long-term oxygen therapy should be prescribed as

clinically indicated since it has been shown to reverse
and /or stabilize PH over a period of 2 to 6 years.
COPD and Pulmonary Hypertension
PAH specific medical therapy including prostacyclin
analogues, phosphodiesterase-5 inhibitors and endothelin
receptor antagonists were tested in randomized controlled
trials, leading to approval of several drugs.

However a recent study included COPD patients with mild

resting PH or no PH treated with Bosentan or placebo
showed no improvement in pulmonary hemodynamics but a
worsening of gas exchange abnormalities.
Thank You