COPD WITH ITS TREATMENT

1. Chronic Obstructive Pulmonary
Disease
DR SHAILESH GUPTA
18/11/17

2. • Chronic obstructive pulmonary disease (COPD) is
• A chronic ,Slowly progressive disorder characterized by
airflow limitation that is not fully reversible.

3. • COPD includes
• Emphysema-- an anatomically defined condition
characterized by destruction and enlargement of the
lung alveoli;
• chronic bronchitis, a clinically defined as a
productive cough that last for 3 months or more for
at least 2 years

4. • chronic bronchitis without chronic airflow
obstruction is not included in COPD.
• COPD is the third leading cause of death and
affects >10 million persons in the United
states

5. PATHOGENESIS
• Airflow limitation, major physiologic change in
COPD,
• result from both small airway obstruction and
emphysema.
• small airways become narrowed by cells
hyperplasia , mucus, and fibrosis.

6. • airway fibrosis due to activation of
transforming growth factor β (TGF-β )
• While lack of TGF-β may contribute to
parenchymal inflammation and emphysema.

7. • pathogenesis of emphysema---
• Chronic exposure to cigarette smoke leads to
•
•
•
• inflammatory and immune cell recruitment
•
inflammatory cells release elastolytic and other proteinases
that damage the extracellular matrix of the lung.

8. Structural cell death (endothelial and epithelial cells)
through oxidant-induced cigarette smoke damage as
well as indirectly via proteolytic loss of matrix
attachment.
•
• Ineffective repair of elastin and other extracellular
matrix components result in air space enlargement
that defines pulmonary emphysema.

10. INFLAMMATION AND EXTRACELLULAR
MATRIX PROTEOLYSIS
• exposure to oxidants from cigarette smoke,
macrophages and epithelial cells become
activated,
• Produce proteinases and chemokines that attract
other inflammatory and immune cells.

11. • Other mechanism of macrophage activation
occurs via
• oxidant-induced inactivation of histone
deacetylase-2, shifting the balance toward
acetylated or loose chromatin.

12. • resulting in transcription of matrix
metalloproteinases, proinflammatory cytokines
such as
• interleukin 8 (IL-8), and
• tumor necrosis factor α (TNF-α);
• this leads to neutrophil recruitment.

13. • CD8+ T cells are also recruited in response to
cigarette smoke and
• release interferon-inducible protein-10 (IP-10),
• leads to macrophage production of macrophage
elastase (matrix metalloproteinase-12 (MMP-12).

14. • cigarette smoke–
• impaired macrophage phagocytosis,
• induced loss of cilia in the airway epithelium
• Which predispose to bacterial infection with
neutrophilia.

15. • Cigarette smoke oxidant-mediated structural cell death
occurs via a variety of mechanisms including
• rt801 inhibition of mammalian target of rapamycin
(mTOR),
• leading to cell death ,inflammation and proteolysis.
• Cigarette smoke impairs macrophage uptake of
apoptotic cells, limit repair.

16. PATHOLOGY
• Cigarette smoke exposure affect ---
• large airways
• small airways (≤2 mm diameter), and
• alveoli.

17. • Changes in large airways cause cough and sputum,
•
• changes in small airways and alveoli are responsible
for physiologic alterations.
• Emphysema and small airway pathology are present
in most persons with COPD;

18. • LARGE AIRWAY—
• Cigarette smoking results in ---
• mucus gland enlargement and
• goblet cell hyperplasia,
• leading to cough and mucus production
• but these abnormalities are not related to
airflow limitation.

19. • Goblet cells not only increase in number but in extent
through the bronchial tree.
• Bronchi undergo squamous metaplasia, predisposing
to carcinogenesis and disrupting mucociliary clearance.
• But not prominent as in asthma, patients.

20. • Patient have smooth-muscle hypertrophy and bronchial
hyperreactivity leading to airflow limitation.
• Neutrophil influx associated with purulent sputum of
upper respiratory tract infections.

21. SMALL AIRWAYS
• The major site of increased resistance in most
individuals with COPD is in airways ≤2 mm diameter.
Characteristic cellular changes include
• goblet cell metaplasia, these cells replacing
• surfactant-secreting Clara cells.
• Smooth-muscle hypertrophy

22. • These abnormalities cause luminal narrowing
by
• fibrosis,
• excess mucus,
• edema, and
• cellular infiltration.

23. Reduced surfactant increase surface tension at the air-
tissue interface, predisposing to airway narrowing and
collapse.
Respiratory bronchiolitis with mononuclear
inflammatory cells collecting in distal airway tissues
cause proteolytic destruction of elastic fibers in
respiratory bronchioles

24. LUNG PARENCHYMA
• Emphysema--- characterized by destruction of gas-
exchanging air spaces, i.e., the respiratory bronchioles,
alveolar ducts, and alveoli.
• Their walls become perforated and obliterated with
coalescence of small air spaces into a larger air spaces.

25. • Macrophages accumulate in respiratory bronchioles of
all young smokers
• In smokers Bronchoalveolar lavage fluid contains five
times macrophages as compare to nonsmokers.

26. • macrophages comprise >95% of the total cell count and
• neutrophils, nearly absent in nonsmokers’ lavage,
account for 1–2% of the cell
• T lymphocytes, particularly CD8+ cells,are also increased
in the alveolar space of smokers.

27. • Emphysema is classified into --
• centriacinar
• panacinar.

28. • Centriacinar emphysema,
• most frequently associated with cigarette smoking,
is characterized by enlarged air spaces.
• Most prominent in the upper lobes and superior
segments of lower lobes

29. • Panacinar emphysema
• abnormally large air spaces evenly distributed
within and across acinar units.
• Panacinar emphysema is usually observed in
patients with α1AT deficiency,
• which has a predilection for the lower lobes.

30. PATHOPHYSIOLOGY
most typical finding in COPD –
• reduction of forced expiratory flow rates .
• Increases residual volume and
• residual volume/total lung capacity ratio,
• and ventilation-perfusion mismatching.

31. AIRFLOW OBSTRUCTION
• Airflow obstruction also known as airflow
limitation
• determined by spirometry,
• involves forced expiratory maneuvers after the
subject has inhaled to total lung capacity.

32. • Key parameters obtained from spirometry
include
• the volume of air exhaled within the first second
of the forced expiratory maneuver (FEV1)
• The total volume of air exhaled during the entire
spirometric maneuver (forced vital capacity
[FVC]).

33. • Patients with airflow obstruction related to COPD
have a chronically reduced ratio of FEV1/FVC.
• In contrast to asthma, the reduced FEV1 in COPD
seldom shows large responses to inhaled
bronchodilators,
• Asthma patients can also develop chronic (not fully
reversible) airflow obstruction.

34. • HYPERINFLATION
• Lung volumes are routinely assessed in pulmonary
function testing.
• In COPD there is “air trapping” (increased residual
volume and increased ratio of residual volume to total
lung capacity) and
• progressive hyperinflation (increased total lung
capacity) late in the disease.

35. • hyperinflation push the diaphragm into a flat position
with a number of adverse effects.
• First, by decreasing the zone of apposition between the
diaphragm and the abdominal wall,
• positive abdominal pressure during inspiration is not
applied as effectively to the chest wall,and impairing
inspiration.

36. Second, because the muscle fibers of the flattened
diaphragm are shorter than those of a more normally
curved diaphragm,
they are less capable of generating inspiratory pressures
than normal.

37. • Third,
• the flattened diaphragm(with increased radius of
curvature, r) generate greater tension (t)
• to develop the transpulmonary pressure (p) required to
produce tidal breathing.
• follows Laplace’s law, p = 2t/r.

38. RISK FACTORS
• 1. CIGARETTE SMOKING—
• cigarette smoking is a major risk factor,
• longitudinal studies have shown accelerated decline in
FEV1 in a dose-response relationship to the intensity of
cigarette smoking,

39. • Which is expressed as pack-years (average number of
packs of cigarettes smoked per day multiplied by the
total years of smoking).
• This dose-response relationship between reduced
pulmonary function and cigarette smoking intensity
• accounts for the higher prevalence rates of COPD with
increasing age.

40. 2. OCCUPATIONAL EXPOSURES—
including
• coal mining,
• cotton textile dust,
risk factors for chronic airflow obstruction.
• coal miners, coal mine dust exposure was a significant
risk factor for emphysema in both smokers and
nonsmokers.

41. 3. AIR POLLUTION—
• increased respiratory symptoms in those living in urban
compared to rural areas, which relate to increased
pollution in the urban.
• Prolonged exposure to smoke produced by biomass
combustion—a common mode of cooking in some
countries—significant risk factor for COPD among
women in those countries.

42. 4.GENETIC CONSIDERATIONS—
• cigarette smoking is the major environmental risk
factor for the development of COPD.
• Severe α1AT deficiency proven genetic risk factor for
COPD;
• α1 Antitrypsin Deficiency --Many variants of the
protease inhibitor (PI or SERPINA1) locus that encodes
α1AT .
• The common M allele is associated with normal α1AT
levels.

43. • The S allele, associated with slightly reduced α1AT
levels, and
• the Z allele, associated with markedly reduced α1AT
levels.
• Individuals with two Z alleles or one Z and
• one null allele are referred as PiZ, which is the most
common form of severe α1AT deficiency.

44. CLINICAL PRESENTATION
The three most common symptoms in COPD are
• cough,
• sputum production,
• and exertional dyspnea.

45. In advances COPD---
• dyspnea on exertion ,and
• breathless doing simple activities of daily living.
• Pursed-lip breathing
• Contraction of the sternomastoid and scalene
muscles on insipiration.

46. CLINICAL PRESENTATION cont--
PHYSICAL FINDINGS
• early stages of COPD, patients usually have an entirely
normal On physical examination.
• Current smokers have signs of active smoking, including
an odor of smoke or nicotine staining of fingernails.
• patients with severe disease, on physical examination
prolonged expiratory phase with expiratory wheezing.

47. • Patients with severe airflow obstruction may also exhibit
use of accessory muscles of respiration, sitting in the
characteristic “tripod” position
• To facilitate the actions of the sternocleidomastoid,
scalene, and intercostal muscles.
• Patients may develop cyanosis, visible in the lips and nail
beds.

48. • patients with predominant emphysema, termed “pink
puffers,” are thin and noncyanotic at rest and have
prominent use of accessory muscles,
• patients with chronic bronchitis are heavy and cyanotic
(“blue bloaters”),

49. • Other feature of Advanced disease
• cachexia, with significant weight loss,
• bitemporal wasting, and
• diffuse loss of subcutaneous adipose tissue.
• This syndrome has been associated with both inadequate
oral intake and elevated levels of inflammatory cytokines
(TNF-α).

50. • patients with advanced disease have paradoxical
inward movement of the rib cage with inspiration
(Hoover’s sign),
• result of alteration of the vector of diaphragmatic
contraction on the rib cage as a result of chronic
hyperinflation.
• Clubbing of the digits is not a sign of COPD

51. LABORATORY FINDINGS
• The hallmark of COPD is airflow obstruction
• Pulmonary function testing shows airflow obstruction
with a reduction in FEV1 and FEV1/FVC ,
• lung volumes may increase, resulting in an increase in
total lung capacity, functional residual capacity, and
residual volume.

52. • In patients with emphysema, the diffusing capacity is
reduced,
• Due to lung parenchymal destruction characteristic of
the disease.
• 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

53. • COPD cannot be diagnosed on a chest radiograph but
useful in excluding other pathology
• In moderate and severe COPD the chest radiograph
typically shows
• Hypertranslucent lung field
• Low flat diaphragams
• Prominent pulmonary artery shadows

54. .
• Increased lung volumes and flattening of the diaphragm
suggest hyperinflation but do not provide information
about chronicity of the changes.
•
• Computed tomography (CT) scan is the current
definitive test for establishing the presence or absence
of emphysema .

55. • Recent guidelines have suggested
• testing for α1AT deficiency in all subjects with COPD
or asthma with chronic airflow obstruction.
• Measurement of the serum α1AT level is a initial test.
• subjects with low α1AT levels, the definitive diagnosis
of α1AT deficiency
• requires protease inhibitor (PI) type determination.

56. • This is typically performed by isoelectric focusing of
serum, which reflects the genotype at the PI locus for
the common alleles and many of the rare PI alleles as
well.
• Molecular genotyping of DNA can be performed for
the common PI alleles (M, S, and Z).

57. TREATMENT
• STABLE PHASE COPD
Only three interventions—
• smoking cessation,
• oxygen therapy in chronically hypoxemic patients,
• and lung volume reduction surgery in selected patients
with emphysema.

58. • All other current therapies are directed at
improving symptoms
• and decreasing the frequency and severity of
exacerbations.

59. • PHARMACOTHERAPY
• Smoking Cessation It has been shown that middle
aged
• smokers who were able to successfully stop smoking
significant improvement in the rate of decline in
pulmonary function,
• returning to annual changes similar to that of
nonsmoking patients.

60. • All patients with COPD should be strongly urged to quit
smoking and educated about the benefits of quitting.
• There are three principal pharmacologic approaches to
the problem:
• 1.nicotine replacement therapy available as gum,
transdermal patch, inhaler, and nasal spray; and

61. • Bupropion—norepinephrine-dopamine reuptake
inhibitor (NDRI) ana nicotinic anatogonist,
• It reduces the nicotine craving and withdrawal
symptom.
• Epileptic seizures are the most common side effect
• varenicline--a nicotinic acid receptor
agonist/antagonist– it reduces cravings and
decreases the plesurable effect of tobacco products.

62. • Food and drug administratio (FDA) approved the use
of vernicline for up to 12 weeks
• If smoking cessation has been achieved continued
another twelve weeks.
• Mild nausea is the most common side effect
• And other common side effect include-
headche,difficulty sleeping and nightmares

63. • Bronchodilators—
• bronchodilators are used for symptomatic patients with
COPD.
• inhaled route is preferred for medication delivery
because the incidence of side effects is lower
• than that seen with the use of parenteral medication
delivery.

64. • Anticholinergic Agents—
• Ipratropium bromide improves symptoms and produces
acute improvement in FEV1.
• Tiotropium-- long-acting anticholinergic, has been
shown to improve symptoms and reduce exacerbations.
• Studies of both ipratropium and tiotropium have failed
to demonstrate that either influences the rate of decline
in FEV1.

65. --
• Beta Agonists—
• provide symptomatic benefit.
•
• Long-acting inhaled β agonists, such as salmeterol or
formoterol, and more effective than ipratropium
bromide.
• The main side effects are tremor and tachycardia

66. • Glucocorticoids—
• chronic use of oral glucocorticoids for treatment of
COPD is not recommended because of an unfavorable
benefit/risk ratio.
Inhaled Glucocorticoids associated with
• increased rates of oropharyngeal candidiasis
• and increased rate of loss of bone density

67. The chronic use of oral glucocorticoids is associated with
significant side effects,
• including osteoporosis,
• Weight gain,
• cataracts,
• glucose intolerance,
• and increased risk of infection..

68. Theophylline—
• Theophylline improve expiratory flow rates and vital
capacity
• and improvement in arterial oxygen and carbon dioxide
levels in patients with moderate to severe COPD.

69. • Nausea
• tachycardia and
• Tremor
• is a common side effect
roflumilast--
• is selective phosphodiesterase4 (PDE4) inhibitor
• used to reduce exacerbation frequency in COPD
patients with chronic bronchitis and a prior history of
exacerbations;

70. Oxygen—
• Supplemental O2 is commonly prescribed for patients
with exertional hypoxemia and nocturnal hypoxemia.
• And patients with resting hypoxemia (resting O2
saturation ≤88% or <90% with signs of pulmonary
hypertension or right heart failure).

71. • Other Agents—
• N-acetyl cysteine used in patients with COPD for both
its mucolytic and antioxidant properties.
• Specific treatment in the form of IV α1AT augmentation
therapy is available for individuals with severe α1AT
deficiency.
• α1AT augmentation therapy is not recommended for
severely α1AT-deficient persons with normal
pulmonary function and a normal chest CT scan.

72. • Lung Transplantation—
• COPD is currently the second leading indication for lung
transplantation.
• Current recommendations are that candidates for lung
transplantation
• should have severe disability despite maximal medical
therapy and
• be free of comorbid conditions such as liver, renal, or
cardiac disease.

73. TREATMENT OF ACUTE EXACERBATIONS—
Bronchodilators
• patients are treated with an inhaled β agonist, with the
addition of an anticholinergic agent.
• the frequency of administration depends on the
severity of the exacerbation.
• Patients are often treated initially with nebulized
therapy, as such treatment is easier to administer in
older patients or in respiratory distress.

74. Oxygen
• Supplemental O2 should be supplied to keep arterial
saturations ≥90%.
• 24-28% via mask ,2 litres/min by nasal prong
check ABGs within 60 min and adjust according to
pao2 and paco2/pH

75. Glucocorticoids—
• the use of glucocorticoids
• reduce the length of stay, and
• reduce the chance of subsequent exacerbation or
• relapse for a period of up to 6 months.
• The GOLD guidelines recommend--
30–40 mg of oral prednisolone or its equivalent for a
period of 10–14 days.

76. Mechanical Ventilatory Support—
• noninvasive positive pressure ventilation (NIPPV) in
patients with respiratory failure, results in a significant
reduction in
• mortality rate,
• need for intubation,
• complications of therapy, and
• hospital length of stay.

77. Invasive (conventional) mechanical ventilation via an
endotracheal tube is indicated for patients with severe
respiratory distress despite initial therapy,
• life-threatening hypoxemia,
• severe hypercarbia and/or acidosis,
• markedly impaired mental status,
• Respiratory arrest,
• hemodynamic instability, or other complications.

78. THANK YOU