CHRONIC OBSTRUCTIVE

PULMONARY DISEASE
CASE

IDENTIFYING DATA:

JT, 46-yr old, married, roman catholic, traffic enforcer from

Silang, Cavite

Informant: Self
Reliability: 90%
CASE

CHIEF COMPLAINT:

Difficulty of Breathing
 CASE

HISTORY OF PRESENT ILLNESS:

3 months PTC, patient started to have productive cough with about ½ tablespoon
of sputum each bouts and associated with shortness of breath doing his usual
ADLs. No consult done. Patient self-medicated with Carbocisteine (Solmux)
500mg/tab taken 3x a day which provided mild relief taken for 5 days only.
CASE

HISTORY OF PRESENT ILLNESS:

Symptoms persisted until few hours PTC, while at work, patient experienced difficulty of
breathing which prompted consult.
 CASE

PAST MEDICAL HISTORY:

(+) Hypertension since 2015, maintained on Losartan 50mg/tab OD

(-) DM, BA, TB

(-) Allergies

(-) Surgical interventions

CASE

FAMILY HISTORY:

(+) Hypertension, Maternal side

(+) Lung CA, Father, died last 2014

(-) DM, BA
 CASE
SOCIAL HISTORY:

Happily married for 20 years with 3 children.

Traffic enforcer for 8 years

(+) Smoker, 5sticks/day for 26yrs, 7pack years, quit 3 months ago when he started having cough

(+) Alcohol beverage drinker, drinks 1 bottle of beer 2-3x/week

(-) Illicit drugs use

Diet: mostly meat, rice and vegetables

CASE
REVIEW OF SYSTEMS
GENERAL: Denies weight loss, fever and chills.

HEENT: Denies changes in vision and hearing.

RESPIRATORY: Dyspnea on exertion.

CV: Denies palpitations

GI: Denies abdominal pain, nausea, vomiting and diarrhea.

GU: Denies dysuria and urinary frequency.

MSK: Denies myalgia and joint pain.

SKIN: Denies rash and pruritus.

NEUROLOGICAL: Denies headache and syncope.

PSYCHIATRIC: Denies recent changes in mood. Denies anxiety and depression.

CASE
PHYSICAL EXAMINATION
GENERAL: Heavy-built man. Alert, awake and oriented. In tripod position. In respiratory distress.

SKIN: No rashes or lesions. (+) pallor

EYES: EOMI

HENT: (+) Cyanosis noted on lips. No cervical lymphadenopathy.

LUNGS: (+) expiratory wheeze. Long expiration

CARDIOVASCULAR: Tachycardic. No murmur. No JVD.

ABDOMEN: Soft, non-tender and globular. No palpable masses.

EXTREMITIES: No edema. Non-tender.

NEUROLOGIC: No focal neurological deficits. CN II-XII grossly intact

PSYCHIATRIC: Cooperative. Appropriate mood and affect

CASE

VITAL SIGNS

BP: 140/90 Height: 5’9”

HR: 115bpm
Weight: 82kg
RR: 20cpm

Temp: 37.1°C BMI: 26.7kg/m2;

O2Sat: 93% on RA
Overweight
 CASE

SALIENT FEATURES:

46-year old

Traffic enforcer for 8 years

3-month history of productive cough, ½ cup phlegm each bout

Progressive shortness of breath

Hypertensive

Smoker, 7 pack years

No weight loss
Dyspnea on exertion
Pallor, cyanosis of lips
Expiratory wheeze, Long expiration
ADMITTING DIAGNOSIS:

COPD t/c Chronic Bronchitis r/o Emphysema

CASE

LABORATORY WORK UP

CBC
RESULT REFERENCE RANGE
WBC 5.4 x 10³/mm³ 4-10 x 10³/mm³
HGB 13.8g/dL 13.8-17.2g/dL
HCT 42% 40.7-50.4%
PLT 195 140-440 x 10³/uL
CASE

LABORATORY WORK UP

Serum electrolytes, clotting factors, liver function test are within normal limits.
CASE

Xray
Remarks:
- enlarged lungs
- flattened diaphragm

Impression:
COPD
 CASE

PRE- POST
TEST BRONCHODIL BRONCHODIL
ATOR ATOR

FVC 2.5 2.95

Lung Spirometry
FVC% 79% 93%

FEV1 1.15 1.55

FEV1% 54% 73%

FEV1/FVC 50% 67.4%

 DIFFERENTIAL DIAGNOSIS

RULE IN RULE OUT

CHRONIC BRONCHITIS Dyspnea
Cough
Wheezing
Productive cough
ASTHMA Dyspnea (-) Family history of asthma
Wheezing (-) Signs of atopy
(+) productive cough
(-) Nocturnal symptoms
TUBERCULOSIS Cough (-) Weight loss
Dyspnea (-) Fever
(-) Night sweats
(-) Hemoptysis
LUNG CA Cough (-) hemoptysis
Dyspnea (-) weight loss
(-) hoarseness
(-) fatigue
FINAL DIAGNOSIS:

CHRONIC BRONCHITIS
 CHRONIC
OBSTRUCTIVE
PULMONARY DISEASE
 CHRONIC OBSTRUCTIVE PULMONARY DISEASE
a disease state characterized by persistent respiratory symptoms and airflow limitation
that is not fully reversible.

requires the presence of chronic airflow obstruction, determined by

spirometry, that usually occurs in the setting of noxious environmental
exposures--------
most commonly cigarette smoking
 COPD
CHRONIC
EMPHYSEMA
BRONCHITIS SMALL AIRWAY DISEASE

clinically
an anatomically
defined condition
definedwith condition in which small
condition
chronic cough
characterized
and phlegm
by bronchioles are narrowed and
destruction of the lung alveoli reduced in number
with air space enlargement
COPD: EPIDEMIOLOGY

COPD is a disease of increasing public health importance around the world.

7TH LEADING CAUSES OF DEATH IN THE PHILIPPINES IN 2017

Estimates that COPD will rise to the third most common cause of death worldwide by 2020.
COPD:
PATHOGENESIS
 COPD: PATHOGENESIS

Airflow limitation - major physiologic change

Small airways become narrowed by cells (hyperplasia and accumulation), mucus,

and fibrosis, and extensive small airway destruction has been demonstrated to be
a hallmark of COPD.
EMPHYSEMA
 INFLAMMATION AND EXTRACELLULAR
MATRIX PROTEOLYSIS

Elastin - the principal component of elastic fibers, is a highly stable component of

the extracellular matrix that is critical to the integrity of the lung

Elastase:antielastase hypothesis, proposed in the mid-1960s - postulated that the

balance of elastin-degrading enzymes and their inhibitors determines the
susceptibility of the lung to destruction resulting in air space enlargement.
ELASTASE:ANTIELASTASE HYPOTHESIS
Lung macrophages
and epithelial cells IL-8 and TNF-α activated leads
become activated, Elastase is
to neutrophil recruitment and
producing proteinases increased,
CD8+ T cells and release
and chemokines that overpowering the
interferon-inducible protein-10
attract other antielastase,
(IP-10, CXCL-7), which leads
inflammatory and degrades the
to macrophage production of
immune cells elastic capacity of
macrophage elastase (matrix
the lungs
metalloproteinase-12 [MMP-
12], most notably neutrophil
elastase
CELL DEATH

Cigarette smoke oxidant-mediated leads to cell death as well as inflammation and

proteolysis.

Involvement of mTOR and other senescence markers has led to the concept that
COPD resembles premature aging of the lung.
 INEFFECTIVE REPAIR

Replace of lost smaller airways and microvasculature and damaged alveoli is

limited. Uptake of apoptotic cells by macrophages results in production of growth
factors that dampens inflammation, promoting lung repair.

Cigarette smoke impairs macrophage uptake of apoptotic cells, limiting repair.

 COPD:
PATHOLOGY
COPD: PATHOLOGY

Cigarette smoke exposure may affect the lungs in different anatomical parts.

In large airways it causes cough and sputum production, while changes in small
airways and alveoli are responsible for physiologic alterations
LARGE AIRWAYS

Cigarette smoking leads to

mucus gland enlargement and
goblet cell hyperplasia, leading
to cough and mucus production
that define chronic bronchitis,
but these abnormalities are not
related to airflow limitation.
 SMALL AIRWAYS

The major site of increased resistance in most individuals with COPD is in airways ≤2 mm
diameter.

 Goblet cell metaplasia, replacing surfactant-secreting Club cells

 Smooth-muscle hypertrophy may also be present
 Luminal narrowing by fibrosis, excess mucus, edema, and cellular infiltration.
 Increased surface tension at the air-tissue, predisposing to airway narrowing or
collapse.
 LUNG PARENCHYMA

Large numbers of macrophages accumulate in respiratory bronchioles of essentially all

smokers.

Bronchoalveolar lavage fluid from such individuals contains roughly five times as many
macrophages as lavage from nonsmokers. Neutrophils and T lymphocytes, particularly
CD8+ cells, are also increased in smokers.
LUNG PARENCHYMA

Emphysema is classified into distinct pathologic types, which include centrilobular,

panlobular, and paraseptal.
 COPD:
PATHOPHYSIOLOGY
 AIRFLOW OBSTRUCTION
Airflow obstruction, is typically determined for clinical purposes by spirometry, which involves forced
expiratory maneuvers after the subject has inhaled to total lung capacity.

Key parameters obtained:

FEV1
FVC

Patients with airflow obstruction related to COPD have a chronically reduced ratio of FEV1/FVC.
HYPERINFLATION

In COPD there is often “air trapping” (increased residual volume and increased ratio of
residual volume to total lung capacity) and progressive hyperinflation (increased total
lung capacity)
HYPERINFLATION

Despite compensating for airway obstruction, hyperinflation can push the diaphragm
into a flattened position with a number of adverse effects.

 First, positive abdominal pressure during inspiration is not applied as effectively

to the chest wall, hindering rib cage movement and impairing inspiration.
 Second, they are less capable of generating inspiratory pressures than normal.
 Third, the flattened diaphragm must generate greater tension to develop the
transpulmonary pressure required to produce tidal breathing.
 Fourth, during tidal breathing the inspiratory muscles must do work to overcome
the resistance of the thoracic cage to further inflation instead of gaining the
normal assistance from the chest wall recoiling outward toward its resting
volume.
GAS EXCHANGE

The partial pressure of oxygen in arterial blood Pao2 usually remains near normal
until the FEV1 is decreased to ~50% of predicted, and even much lower FEV1 values
can be associated with a normal Pao2, at least at rest.

An elevation of arterial level of carbon dioxide (Paco2) is not expected until the FEV1
is <25% of predicted and even then may not occur.
 GAS EXCHANGE

Non-uniform ventilation and ventilation-perfusion mismatching are characteristic of COPD

This Ventilation-perfusion mismatching accounts for essentially all of the reduction in

Pao2 that occurs in COPD and explains the effectiveness of modest elevations of inspired
oxygen in treating hypoxemia due to COPD
 COPD:
RISK FACTORS
 CIGARETTE SMOKING

•accelerated decline in FEV in a dose-response relationship to the intensity of cigarette smoking

•typically expressed as pack-years (average number of packs of cigarettes smoked per day
multiplied by the total number of years of smoking)

•additional environmental and/or genetic factors contribute to the impact of smoking on the
development of airflow obstruction
AIRWAY HYPERRESPONSIVENESS

•surrogate marker of airway obstruction in COPD

•Dutch hypothesis suggests that asthma, chronic bronchitis, and emphysema

are variations of the same basic disease, which is modulated by
environmental and genetic factors to produce these pathologically distinct
entities
 RESPIRATORY INFECTIONS

•important causes of exacerbations of COPD

•both adult and childhood respiratory infections with the development and progression of COPD
remains to be proven.

•But conditions like chronic bronchitis, pneumonia, childhood respiratory illness has not been
significantly causing decline in pulmonary function, which is yet to be proven by longitudinal
studies.
 OCCUPATIONAL EXPOSURES

•exposure to dust and fumes at work. Several specific occupational exposures,

including coal mining, gold mining, and cotton textile dust, have been suggested as risk
factors for chronic airflow obstruction
AMBIENT AIR POLLUTION

•Not a strong risk factor but has been seen on women who are exposed to continuous
smoke while cooking on urban part of the worlds.
SECOND HAND SMOKING

•Exposure of children to maternal smoking results in

significantly reduced lung growth.
•In utero, tobacco smoke exposure also contributes to
significant reductions in postnatal pulmonary function.
 GENETIC PREDISPOSITION

•Alpha 1 antitrypsin deficiency – Mutation in serpina1 gene

•approximately 1% of COPD patients are found to have

severe α1 AT deficiency as a contributing cause of COPD,

•these patients demonstrate that genetic factors can have a

profound influence on the susceptibility for developing
COPD
NATURAL HISTORY OF
COPD
DEVELOPMENT OF COPD DEPENDS ON:

•Intensity of smoking
exposure
•the timing of smoking

•exposure during growth

•the baseline lung function

•other environmental
factors
COPD:
CLINICAL
MANIFESTATION
 HISTORY

•Three most common symptoms are : cough, sputum production,dyspnea on exertion

•date the onset of their disease to an acute illness or exacerbation

•Activities involving significant arm work, particularly at or above shoulder level, are particularly
difficult for patients with COPD

•Conversely, activities that allow the patient to brace the arms and use accessory muscles of
respiration are better tolerated

•resting hypoxemia Can be seen as disease progresses

PHYSICAL FINDINGS

•In the early stages of COPD,

patients usually have an entirely
normal physical examination
•patients with more severe disease
•a prolonged expiratory phase and
may include expiratory wheezing. In
•signs of hyperinflation include a
barrel chest and enlarged lung
volumes
• poor diaphragmatic excursion can
assessed by percussion.
 PHYSICAL FINDINGS

•Patients with severe airflow obstruction

may
• exhibit use of accessory muscles of
respiration, sitting in the characteristic
“tripod” position .
•Patients may develop cyanosis, visible in
the lips and nail beds
PINK PUFFERS VS BLUE BLOATERS

•Pink puffers and blue Bloaters

•emphysema, termed “pink
puffers,” are thin and noncyanotic
at rest and have prominent use of
accessory muscles, patients with
chronic bronchitis are more likely
to be heavy and cyanotic (“blue
bloaters”)
 PHYSICAL EXAMINATION

•weight loss, bitemporal wasting, and diffuse

loss of subcutaneous adipose tissue shows
advanced disease progression

•paradoxical inward movement of the rib cage

with inspiration (Hoover’s sign), the result of
alteration of the vector of diaphragmatic
contraction on the rib cage as a result of
chronic hyperinflation
LABORATORY FINDINGS

•Pulmonary function testing

shows airflow obstruction with a
reduction in FEV1 and FEV1/FVC
.
•Arterial blood gases and
oximetry may demonstrate
resting or exertional hypoxemia
 LABORATORY FINDINGS

•elevated hematocrit suggests the presence of chronic hypoxemia

•Radiographic studies may assist in the classification of the type of COPD.

•Obvious bullae, paucity of parenchymal markings, or hyperlucency suggests the presence
of emphysema.
• Increased lung volumes and flattening of the diaphragm suggest hyperinflation
LABORATORY FINDINGS

•CT scan is the current definitive test for establishing the

presence or absence of emphysema in living subjects
•CT scan currently does little to influence therapy of COPD
except in individuals considering surgical therapy
•Measurement of the serum αlpha 1 antitrypsin AT level is a
reasonable initial test
 COPD:
TREATMENT
COPD: TREATMENT

 Two main goals:

 Provide symptomatic relief
 Reduce future risk
 STABLE PHASE COPD

COPD severity assessment

 mMRC – Modified Medical Research Council
Dyspnea Scale

It provides a single number for degree of breathlessness

- 0 : only with strenuous activity
- 1: hurrying on level ground or walking up a slight hill
- 2: walk slower than peers or stop walking at their own pace
- 3: walking about 100 yards (91 meters) or after a few minutes on level
ground
- 4: too breathless to leave the house or when dressing
CAT – COPD Assessment Test
MEDICATION THERAPY
Group A
- All patients should be offered bronchodilator treatment based on its effect on breathlessness.
It can be either short acting or long acting bronchodilator
- Continue if benefit is documented

Group B
- Should consist of long acting bronchodilator
- No evidence to recommend one class of long acting bronchodilators over another. It should
depend on patient’s perception of symptoms relief
- Severe breathlessness = two bronchodilators
Group C
- Consist of a single long acting bronchodilator. In two head to head comparison, LAMA > LABA
regarding exacerbation prevention.

Group D
LAMA has effects on both breathlessness and exacerbations
For severe symptoms (CAT > 20) = LAMA + LABA
Blood eosinophil counts >300 cells/uL = LABA + ICS to reduce exacerbations
PHARMACOTHERAPY

Smoking Cessation
Three pharmacological approaches

 Nicotine replacement therapy: gums, transdermal patch, lozenge, inhaler and nasal spray

 Bupropion – nicotine receptor noncompetitive antagonist

 Varenicline – nicotinic receptor agonist

BRONCHODILATORS

In general, primary treatment for almost all patients with COPD (symptomatic relief and
exacerbations inhaled route preferred mode of delivery (decrease side effects)
 ANTICHOLINERGIC MUSCARINIC ANTAGONIST

IPRATROPIUM BROMIDE – short acting, improves symptoms and provide acute improvement in FEV1

LAMA (Aclidinum, Glycopyrolate, Tiotropium and Umeclidium) – improves symptoms and reduce
exacerbations

Side effects: Dry mouth, most frequent

BETA AGONISTS
Short acting – ease symptoms with acute improvement in lung functions

LABA – provide symptomatic benefit and reduce exacerbations though to a lesser extent than
LAMA

LABA (Arformoterol, Formoterol, Indacaterol, Olodaterol, Salmeterol and Vilanterol)

Main side effects: Tremor and Tachycardia

 INHALED CORTICOSTEROIDS

Main role is to reduce exacerbations

Can be considered in patient with frequent exacerbations (two or more per year) and in
patient with features of asthma, such as eosinophilia

Associated with increase rates of oropharyngeal candidiasis, loss of bone density and
pneumonia
OTHERS:

THEOPHYLLINE – modest improvement in airflow and vital capacity but is not a first line
therapy due to side effects and drug interactions

PDE4 INHIBITORS – reduce exacerbation frequency in severe COPD, Chronic bronchitis and
prior history of exacerbations

ANTIBIOTICS (Azithromycin) – there are strong data implicating bacterial infection as

precipitant of substantial portion of exacerbations
- OXYGEN – Supplemental oxygen is the only pharmacologic therapy demonstrated to unequivocally
decrease mortality rates in patient with COPD
- For resting hypoxemia <88% or
- With signs of pulmonary hypertension

- a1AT AUGMENTATION THERAPY – for severe a1 AT deficiency. Eligibility for this therapy requires a
serum AT level >11uM (50mg/dL).
NON PHARMACOLOGIC THERAPIES

VACCINES – Influenza, Pneumococcal and Bordetella pertussis

PULMONARY REHABILITATION – improves quality of life, dyspnea and exercise

capacity. It has also shown to reduce rate of hospitalization over 6 to 12 month
period
LUNG VOLUME REDUCTION SURGERY – improves exercise, lung function and survival. Beneficial
for patient with upper lobe predominant emphysema and low post rehab exercise capacity

LUNG TRANSPLANTATION – Candidates are very severe airflow limitation, severe disability despite
maximal medical therapy and free of significant comorbid condition such as liver, renal, or cardiac
disease.
EXACERBATIONS OF COPD

Exacerbations are episodic acute worsening of respiratory symptoms, including:

- Dyspnea
- Cough
- Wheezing
- Change in amount and character of sputum
- May or may not have fever, myalgias and sore throat

Strongest single predictor of exacerbations is a history of a previous exacerbation

Frequency of exacerbations increase as airflow obstruction worsens;
- Severe :FEV1 <50% predicted or very severe FEV1 <30% predicted both have 1-3
episodes per year

Elevated ratio of diameter of pulmonary artery to aorta on chest CT, and gastroesophageal
reflux are also associated with increased risk of exacerbations
 PRECIPITATING CAUSES

- Acquiring new strain of bacteria is associated with increased new term risk of
exacerbation
- Bacterial infection/ superinfection is involved in >50% of exacerbations
- Viral resp. infections present 1/3 of COPD exacerbations
- 20-35%, no specific precipitant can be identified
 TREATMENT OF ACUTE EXACERBATIONS

- Bronchodilators – inhaled B agonist and muscarinic antagonist

- Treated initially with nebulized therapy (due to ease of administration in resp. distress)

- Antibiotics – (Aminopenicillin-Clavulanate, Macrolide, Tetracycline),

- Moderate or severe exacerbations are usually treated even in absence of a specific
pathogen
- Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma
pneumoniae and Chlamydia pneumoniae
- Systemic glucocorticoids – 30-40mg oral prednisolone for 5-10 days in outpatient
- reduce length of stay, hasten recovery and reduce chance of exacerbations.
- Can cause Hyperglycemia in patient with preexisting diagnosis of diabetes

- Oxygen – supplemental oxygen should be supplied to maintain saturation >90%

- Mechanical Ventilatory Support – Non - invasive positive pressure ventilation (NIPPV) and
Invasive (conventional) mechanical ventilation via endotracheal tube.

- NIPPV for patient with respiratory failure, defined as Paco2 >45 mmHg, results in
significant reductions in:
- Mortality rate
- Need for intubation
- Complication of therapy
- Hospital length of stay
- Contraindications to NIPPV:
- Impaired cardiovascular instability
- Impaired mental status
- Inability to cooperate
- Copious secretions or inability to clear secretions
- Craniofacial abnormalities or trauma
- Extreme obesity
- Significant burns
- Invasive (conventional) mechanical ventilation via endotracheal tube is indicated for:
- Severe respiratory distress despite initial therapy
- Life – threatening hypoxemia
- Severe hypercarbia and/or acidosis
- Markedly impaired mental status
- Respiratory arrest
- Hemodynamic instability