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Understanding Chronic Obstructive Pulmonary Disease (COPD)

(Incidence, disease, causes, symptoms & treatment options)

& The role of Metadec in COPD

From: Amit Arora Date:11/9/2006

Prevalence of COPD - World over

COPD affects up to 1 in 10 adults over the age of 40*

Ranks as the fourth leading cause of death worldwide, trailing behind CVD, pneumonia & HIV/AIDS**

Expected to be the third leading cause of death by 2020

Death rate in 2000- Males 56.7/1lac, Females 82.6/1lkh

*Eur Res J, Sept 06- **

Prevalence of COPD - Indian scenario

Approximately 14 million Indians are currently suffering from COPD*

Currently there are 94 million smokers in India

10 lakhs Indians die every year due to smoking related deaths

*The Indian J Chest Dis & Allied Science 2001;43:139-47

COPD Economic burden

Direct cost Medications/ health care cost

Indirect cost Missed work/ premature mortality/ family cost

Future of COPD

COPD is expected to grow globally 1. Due to increase in life expectancy of the population more than 60 yrs 2. Increased usage of cigarette smoking

*American Thoracic Society

COPD - Definition

Is a preventable & treatable disease

Characterized by airflow limitation of the lungs that is not fully reversible

Airflow is usually progressive & is associated with inflammatory response of the lungs to noxious particles or gases primarily caused by smoking

*American Thoracic Society

Sub classes of COPD

Chronic Bronchitis- Chronic or ongoing cough not caused by any other

condition like allergy, infection etc which produces sputum for 3 or more months and is observed during 2 consecutive years

Emphysema- Characterized by permanent enlargement of alveoli, the

alveoli are unable to deflate & unable to fill with fresh air because pockets of dead air in the damaged lung area limits the normal lung functioning

*American Thoracic Society

Physical signs of COPD

1. Large barrel shaped chest 2. Prominent accessory respiratory muscles in neck are used for respiration 3. Low flat diaphragm 4. Diminished breath sound

Diagnosis of COPD

Should be considered in any individual who has 1. Symptoms of cough 2. Sputum production 3. Dyspnoea 4. History of exposure to risk factors for the disease 5. Family history of chronic respiratory illness

*American Thoracic Society

Detecting COPD

1. Air containing volume of the lung 2. The ability to move air into & out of the lung 3. The rate at which gases diffuse between the lung & blood 4. Blood levels of oxygen & carbon dioxide

Detecting COPD

Spirometry test should be done in patients who have

Exposure to cigarettes/ environmental pollution Family history of chronic respiratory illness Presence of cough/sputum/dyspnoea

COPD- A under diagnosed disease

Despite the burden of COPD it has received limited recognition from both patients & physicians*

More than half of the COPD patients are misdiagnosed or treated as having asthma**

*Resp Med 2002;96;S2-s12 **News-Misdiagnosis of COPD- national Jewish medical research center

Why COPD is misdiagnosed as asthma

Both are characterized by airflow limitation

Explosive research on asthma v/s little research in COPD

High awareness levels on asthma v/s low awareness on COPD

But pathogenically & therapeutically they are different

COPD v/s Asthma

Age Starts at 40 yrs

Starts at any age Sniffing, nasal discharge Can be linked to few Specific trigger factors (symptoms are not consistent) Inhaled corticosteroids & if needed addition of bronchodilators

Nasal symptoms Rarely present with nasal symptoms Smoking Triggers 80% of patients are smokers Respiratory tract infections Quitting smoking helps (symptoms are consistent) Bronchodilators

1st line of treatment

COPD v/s Asthma

Chronic Bronchitis Main cause of airflow limitation Mucous hypersecretion
Fibrosis Inflammation

Inflammation Airway hyperresponsiveness

Destruction of alveolar walls Reduced elasticity & recoiling of capillaries for gas exchanges

Narrowing of bronchi & bronchioles

Reversibility Inflammation

Minimal to no reversibility Yes but rarely responsive to antiinflammatory therapy

Mostly reversible Yes, responsive to antiinflammatory therapy Adrenergic/sympathetic responds to adrenergic bronchodilators

Nervous system Cholinergic/parasympathetic control Responds to anticholinergic bronchodilators

Conditions that are not clubbed under COPD

Poorly reversible airflow limitations associated with cystic fibrosis & fibrosis due to tuberculosis are not included in the definition of COPD but should be considered in differential diagnosis

*American Thoracic Society

Pathophysiology of COPD in chronic bronchitis

Bronchial gland hypertrophy Leads to excessive mucous production

Results in chronic bronchitis

As the disease progress there is fibrosis & increased deposition of collagen in the walls resulting in loss of cilia function

Pathophysiology of COPD in emphysema

Persistent inflammation of airspaces due to smoking Abnormal enlargement of alveoli

Significant loss of alveolar attachments

Contributes to peripheral airway collapse

Risk factors for COPD- Host factors

1. Genetic factor- hereditary deficiency of alpha1 antitrypsin, a inhibitor of protease 2. Sex- More prevalent in males 3. Airway hyperresponsiveness

*American Thoracic Society

Risk factors for COPD- Exposure

1. Smoking (lowers the maximally attainable lung function in adulthood) 2. Socioeconomic status (indoor cooking in rural areas using biomass,
impaired growth of lungs, inc rate of infection)

3. Occupation (COPD attributable to work is 19.2%) 4. Environmental pollution 5. Recurrent pulmonary infections 6. Diet

*American Thoracic Society

Smoking the main culprit of COPD

According to WHO 75% of deaths from COPD that occur in developed countries are directly related to smoking *

Smokers are more likely to have upper & lower respiratory tract infections than nonsmokers

The lung functions deteriorates faster in smokers than in nonsmokers

*Eur Res J, Sept 06-

Smoking the main culprit of COPD

1. Contributes to inflammatory response 2. Leads to exaggeration of normal protective inflammatory response leads to tissue destruction impairs defence mechanisms 3. Also leads to imbalance of proteinase & antiproteinase in the lungs - Positioning for Metadec 4. Oxidative stress Positioning for LycoRed

Proteinase & antiprotease imbalance in COPD

Increased activity of proteinase (enzyme for protein degradation) or inactivation of antiproteinase

Inflammatory cells (macrophages, neutrophils) release a combination of proteinase and on the other hand decrease the activity of antiproteinases by oxidation due to free radicals

Oxidative stress in COPD

Presence of Oxidative stress markers evident from the exhaled air from the lungs & urine of smokers

Oxidative stress in COPD

Free radicals Oxidizes variety of biological molecules Leads to cell dysfunction & death Damages the extra cellular matrix Activates proteinases

Mucous hypersecretion , airflow limitation, gas exchange abnormalities

Stages of COPD

Stage 1: lung function at 50% of normal capacity or higher; health is not greatly affected Stage 2: Lungs function at 35-49% of normal capacity; health is significantly impacted Stage 3: Lung function at less than 35%; health is severely affected

Treatment approach to COPD- Algorithm

A. B. C.

Primary care Level (Primary health centers, dispensaries, general practice clinics) Secondary Care Level (District level hospitals and clinics Tertiary Care Level (Medical colleges, large corporate, institutional and specialty hospitals)

Management of COPD

1. Bronchodilators 2. Glucocorticoids (leads to osteoporosis, cataract, muscle weakness and diaphragm


3. Mucolytic 4. Antioxidant therapy (only on N-acetylcysteine-reduces the nos of exacerbations) 5. Antibiotic therapy 6. Oxygen treatment 7. Anabolic steroids for pulmonary rehabilitation

COPD Pulmonary rehabilitation

Exercise training- endurance (aerobic) & strength exercises Education- self management & adherence to the treatment plan Psychosocial & behavioral intervention- Anxiety & depression is
common in these patient Nutritional & Anabolic Therapy Weight loss & muscle wasting are present in 25-30% of the stable patients but it contributes to morbidity & mortality

COPD A disease beyond lungs

Heart disease : Occurs if low oxygen levels develop in the blood it leads to strain on the heart, making it work harder ultimately results in heart diseases & heart attacks

Sleep disorders: leads to sleep disorder, insomnia, nightmares and chronic fatigue

COPD A disease beyond lungs

Skeletal muscle wasting: The systemic effects limits the exercise capacity of the patients and worsens the prognosis leading to skeletal muscle wasting as Weight loss & being underweight are associated with decreased diffusing capacity

Assessment of Body composition

1. Nutritional screening

2. BMI-weight(Kg)/height (m2)
Underweight (BMI<21 kg.m-2) Normal weight (BMI 21-25 kg.m-2) Overweight (BMI 25-31 kg.m-2)

Pathogenesis of weight loss & muscle wasting in COPD

Elevated energy metabolism and increased resting energy has been observed in patients of COPD, due to inflammation & protein turnover 1. Weight loss despite of normal energy intake 2. Inflammatory responses may affect the appetite & dietary intake

Factors affecting muscle wasting in COPD

1. Reduced or altered contractile activity 2. Negative energy balance due to a) Raised energy expenditure b) Reduced dietary intake 3. Reduced testosterone levels 4. Hypoxia or hypoxaemia & acidosis 5. Glucocorticoids 6. Increased pro-inflammatory cytokines
Eur Resp J 2003;;22 52s-63s

Weight loss an unattended complication

Weight loss is an important determinant of 1. Functional capacity due to muscle atrophy & weakness 2. Health status- reduced exercise tolerance & dyspnoea 3. Mortality 4th leading cause of death & prevalence is further increasing
Loss of fat free mass is observed in 20-40% of patients with COPD

Eur Resp J 2003 52s-63s

Weight loss an unattended complication

Significant weight loss has been found to begin on an average 3.5 years before death

Following the onset of unintended weight loss mortality reaches 30% in 3 years and 50% in 5 years

Chest 2002;122:421-428

Malnutrition & COPD

Malnutrition is associated with severe COPD in * 10-26% OPD patients Upto 47% hospitalized patients with acute respiratory failure

*Chest 1998;jul;114;19-28

Effect of weight gain on COPD

Reversal of weight loss has been associated with improved outcomes, incld inc muscle strength, exercise capacity & survival
Restoration of body weight may be difficult to achieve and to maintain using nutritional intervention alone

Chest 2002;122:421-428

Anabolic steroid an additional mode of intervention

Anabolics have been associated with significant improvement 1. Muscle performance 2. Weight 3. Pulmonary function 4. Reduction in breathlessness
(Oxandrolone 20mg/day for 1month)

Mt sinai J Med 1999; May; 66(3): 201-5

Anabolic steroid an additional mode of intervention

Anabolics are effective adjunct to facilitate weight restoration in patients with COPD
(Oxandrolone 20mg/day for 4month)

Chest 2002;122:421-428

Metadec Anabolic adjuvant to enhance pulmonary function

Mechanism of action

1. Increases muscle mass 2. Erythrpoeitic effect 3. Reverses the diaphragmatic muscle weakness specifically induced by glucocorticosteroids

Chest Nov 2003

Metadec Anabolic adjuvant to enhance pulmonary function

Trial 1 : Chest Nov 2003 Nandrolone decanoate 50mg every 15 days for 8 weeks N=63 male patients

Significant rise in fat free mass compared with placebo Increases maximal breath intake Improvement in muscle function & exercise capacity Significant increase in erythrocyte count results in better oxygen delivery to tissue

Chest Nov 2003

Metadec Anabolic adjuvant to enhance pulmonary function

Trial 1 Safety

No changes in blood pressure No androgenic effects No fluid retention

were noted after Nandrolone decanoate treatment or placebo

Chest Nov 2003

Metadec Anabolic adjuvant to enhance pulmonary function

Trial 1 Efficacy in patients on glucocorticoids

Nandrolone decanoate was able to antagonize the loss of diaphragm force induced by long term low dose methylprednisolone administration

Chest Nov 2003

Metadec Anabolic adjuvant to enhance pulmonary function

Trial 1 Conclusion

A short term course of Nandrolone decanoate had an overall positive effect on the body composition with improvement in muscle function, exercise capacity and improvement in erythropoietic parameters. Also restored the pulmonary impairment attributed to the use of glucocortosteroids

Chest Nov 2003

Metadec Anabolic adjuvant to enhance pulmonary function

Trial 2 : Am J Resp Crit Care Med 1995; oct;1268-1274 Nandrolone decanoate 50mg to men & 25 mg to women, every 15 days for 8weeks N=217 patients

Nutritional supplementation alone predominately increased fat mass whereas anabolic steroid increased muscle mass Respiratory muscle strength improved more in the combination therapy (Nutrition + Nandrolone)

Am J Resp Crit Care Med 1995; oct;1268-1274

Metadec Anabolic adjuvant to enhance pulmonary function

Trial 2 Conclusion

Nutritional supplementation and anabolic steroid resulted in some benefits for patients with moderate to severe COPD

Am J Resp Crit Care Med 1995; oct;1268-1274

Metadec Anabolic adjuvant to enhance pulmonary function

Trial 3: Am Phy Soc 1998


The reduction in diaphragm force generation in the methylprednisolone group was completely abolished by the addition of Nandrolone decanoate

Am Phy Soc 1998

Metadec Anabolic adjuvant to enhance pulmonary function

Trial 4: Eur Resp J 1999


Nandrolone decanoate in part reversed the loss of diaphragm force generating capacity in emphysematous hamsters treated with methylprednisolone & reversed the fiber atrophy completely

Eur Resp J 1999


Not only increases life but also improves quality of life