COPD: Management ..update

dPratap Sagar Tiwari, MD, Internal medicine

Note: this is for MBBS lecture class

Making a diagnosis

• A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum production and a history of exposure to risk factors of the disease.

• Spirometry is required to make the diagnosis in this clinical context; the presence of a post bronchodilator FEV1/FVC <0.70 confirms the presence of persistent airflow limitation and thus of COPD.

• FEV1:the volume of air forcefully expired during the 1st sec after taking a full breath• Forced vital capacity (FVC):the total volume of air expired with maximal force

Treatment line begins after assessment of severity of the condition

Postbronchodilator FEV1/FVC <0.7 defines Airflow limitation

Low risk

High Risk

3 yr mortality =24%

Mmrc : Assess severity of breathlessness

• 0-1 = less breathlessnes

s• >2= more breathlessnes

s

BODE INDEXVariable 0 1 2 3

FEV1 O≥ 65 50-64 36-49 ≤ 35

Dist walked in 6 min (m) E

≥ 350 250-349 150-249 ≤ 149

MRC Dyspnoea scale*

0-1 2 3 4

Body mass index > 21 ≤ 21

BODE score 0-2 =mortality rate of around 10% at 52 mnths, BODE score 7-10=mortality rate of around 80% at 52 mnths.

Management of COPD

• Chronic stable phase COPD• COPD on Acute exacerbation

Chronic Stable phase COPD

•Only three interventions- smoking cessation, oxygen therapy in chronically hypoxemic patients, and lung volume reduction surgery in selected patients with emphysema—have been demonstrated to influence the natural history of patients with COPD.

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

Pharmacotherapy

•Smoking cessation•Bronchodilators

Smoking Cessation

There are 4 principal pharmacologic approaches to the problem:

1. Bupropion.2. Nicotine replacement therapy available as

gum, transdermal patch, inhaler, and nasal spray; and

3. Varenicline, a nicotinic acid receptor agonist/antagonist.

4. Nortriptyline

Bronchodilators

•Anticholinergics•B2 Agonists

Inhaled bronchodilators are the mainstay of COPD management

Note:• However no evidence that regular bronchodilator use

slows deterioration of lung function.• Anticholinergics have a greater bronchodilating effect

than b2 agonists.

B Agonists

• Side effects: tremor and tachycardia

SABA Inhaler /mdi For nebuliser DOA (hr)

Salbutamol 100,200 mcg 5 mg/ml 4-6

LevalbuterolAlbuterolPirbuterolTerbutaline

LABA Inhaler (mcg) Oral DOA (hr)

Salmeterol 25-50 12

FormeterolBambuterolIndacarterol

10-20 mg od

Anticholinergics

• Side effects: urinary retention, and dry mouth,tremor and tachycardia

SAA Inhaler For nebuliser mg/ml

DOA (HR)

Ipratropium 20,40 MDI

0.25-0.5 6-8

Oxitropium 100 MDI

1.5 7-9

LAA Inhaler (mcg)

Oral DOA (hr)

Tiotropium 18 DPI 24

Steroids in Stable Copd

• Inhaled Glucocorticoids• Oral Glucocorticoids

• In COPD, inhaled GCs are used as part of a combined regimen, but should NOT be used as sole therapy for COPD (ie, without long-acting BDs).

• Regular Rx improves symptoms, lung function and quality of life and reduce frequency of exacerbations in COPD with FEV1 <60% but however does not modify long term decline of FEV1 nor mortality .

Inhaled Glucocorticoids

•Their use has been A/W ↑ rates of oropharyngeal candidiasis & an ↑ rate of loss of bone density.

•A trial of inhaled GC should be considered in patients with frequent exacerbations, defined as ≥2/yr, and in pts who demonstrate a significant amount of acute reversibility in response to inhaled BD.

Oral Glucocorticoids

•The chronic use of oral GCs for Rx of COPD is not recommended because of an unfavorable benefit/risk ratio.

•The chronic use of oral GCs is a/W significant side effects, including osteoporosis, weight gain, cataracts, glucose intolerance, & ↑ risk of infection.

Theophylline(methylxanthine)

• Theophylline produces modest improvements in expiratory flow rates and vital capacity and a slight improvement in arterial o2 and Co2 levels in patients with moderate to severe COPD.

• Nausea is a common SE; tachycardia and tremor have also been reported.

• MX are less effective and less well tolerated than long acting inhaled bronchodilators and is not recommended if others r available & affordable.

• Addition of low dose slow release theophylline may be given along with long acting BDs.

Phosphodiesterase 4 inhibitors

•Once a day dosage :No direct bronchodilator activity but has shown to improve FEV1 in pts treated with salmeterol or tiotropium.

•Roflumilast ↓ moderate to severe exacerbations treated with CSs by 15-20 % in pts with ch bronchitis, severe and very severe COPD and a Hx of A/E.

•S/e: nausea, pain abodmen, diarrhea, insomnia• Note: Roflumilast & Theophylline shouldnot be given

together.

Vaccination

•All Patients with COPD should receive the influenza vaccine annually.

•Polyvalent pneumococcal vaccine is also recommended, (in pt ≥65 yrs old or <65 + Fev1 <40 %)

Others

Not recommended in stable copd by ATS, BTS, ETS,GOLD1. Mucokinetics and antioxidants (n-acetylcysteine)2. Antitussive3. vasodilators like nitric oxide 4. Drugs to treat pulmonary hypertension (ETA) 5. Nedochromil (mast cell stabilizer)6. Monteleukast (leukotriene modifier)7. Antibiotics

Others

•Specific treatment in the form of IV a1AT augmentation therapy is available for individuals with severe a1AT deficiency.

•Eligibility for a1AT augmentation therapy requires a serum a1AT level <11 uM (approximately 50 mg/dL).

Oxygen (>15 hrs /day)

• Supplemental O2 is the only pharmacologic therapy demonstrated to unequivocally decrease mortality rates in patients with COPD.

1. PaO2 ≤ 7.3 kPa (55 mmhg) or SaO2 <88%, with or without hypercapnia confirmed twice over a 3 week period.

2. PaO2 :7.3 -8.0 kPa (55-60 mmhg) or SaO2 of 88%, if there is evidence of pulmonary HTN, peripheral edema s/o CCF, or polycythemia (HCT>55%).

Lung Volume Reduction Surgery (LVRS)• Sx to reduce the vol of lung in pts with emphysema was first

introduced with minimal success in 1950s and was reintroduced in the 1990s.

• Patients are excluded if they have significant pleural disease, a pulmonary artery systolic pressure >45 mmHg, extreme deconditioning, congestive heart failure, or other severe comorbid conditions. Patients with an FEV1 <20% of predicted and either diffusely distributed emphysema on CT scan have an increased mortality rate after the procedure and thus are not candidates for LVRS.

• Patients with upper lobe–predominant emphysema and a low postrehabilitation exercise capacity are most likely to benefit from LVRS.

Lung Transplantation

•Current recommendations are that candidates for lung transplantation should be <65 years; have severe disability despite maximal medical therapy; and be free of comorbid conditions such as liver, renal, or cardiac disease.

Treatment line begins after assessment of severity of the condition

Postbronchodilator FEV1/FVC <0.7 defines Airflow limitation

Low risk

High Risk

3 yr mortality =24%

Final: Steps in managementClinical diagnosis

Spirometry

Gold severity stage

Drugs a/t stages

Stage ManagementAll - Avoidance of risk factor(s)

- Influenza vaccination- Pneumococcal vaccination

Stage 1 Short-acting bronchodilator when neededStage 2 Short-acting bronchodilator when needed

Regular treatment with one or more long-acting bronchodilators

Stage 3 Short-acting bronchodilator when neededRegular treatment with one or more long-acting bronchodilatorsInhaled glucocorticoids if significant symptoms, lung function response, or if repeated exacerbations

Stage 4 Short-acting bronchodilator when neededRegular treatment with one or more long-acting bronchodilatorsInhaled glucocorticoids if significant symptoms, lung function response, or if repeated exacerbationsTreatment of complicationsLong-term oxygen therapy if chronic respiratory failureConsider surgical treatments

Important questions for MBBS

• Define COPD and mention its components ?• Pathophysiology of Emphysema and mention the types of

emphysema?• Bed side examination findings of Emphysema ?• List Differential diagnosis of Acute onset of Dyspnea ?• Define Dyspnea and list Modified MRC Dyspnea scale.• List the muscles used for Normal and forceful respiration.• Mention GOLD staging ,the spirometric classification of COPD .• What are the four variables used in BODE index?• Management of Stable phase of COPD.• Management of COPD on Exacerbation.

Terms

• Dyspnea: Dyspnea is a term used to characterize a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity.

• Orthopnea: Dyspnea that worsens in lying flat position and gets relieved by sitting position.

• Platypnea: Dyspnea that is relieved when lying down, and worsens when sitting or standing up.

• Trepopnia: Dyspnea while lying on one side but not on the other

(lateral recumbent position)• Tachypnea: refers to abnormally fast breathing rate.• Bradypnea: refers to abnormally slow breathing rate.

General appearance:

• On GE , my patient who is in upright position (sitting by the edge of the bed),appears to be thinly built ,his bmi is …..kg/m2..

• He is conscious and well oriented to person place and time. His speech is normal can complete a full sentence in one breath and there is no hoarseness in voice.

• Patient is on oxygen therapy via nasal prongs. And there are sputum cup and inhalers by his side.

• There is flaring of ala nasae and purse lip breathing and accessory muscle like sternocledomastoid are active.

• There is supraclavicular hollowing and Tracheal tug is present.• There is also indrawing of intercostal muscles (or retraction of

lowermost intercostal spaces are evident) but however audible noises like wheeze or stridor are not heard from the end of the bed.

General appearance:…continue• The respiration is regular but labored and the rate is 22/m and FET is more than 6 sec.(Respiration : comment on :rate ,rhythm, depth and effort ,If Normal: Respiration is quiet and regular with normal depth and effortless. Rate is 14 /m and FET is less than 6 seconds.)• There is no pallor, no icterus and no cyanosis and oral cavity seems normal. There is

no lymphadenopathy and JVP is not raised .• His bp 120/80 mmhg ,axillary temperature is…and pulse is 80/m seems normal in

volume and character. All peripheral pulses are present and the condition of arterial wall seems normal.

• On examination of Hands• There is no clubbing , no peripheral cyanosis, and no palmar erythema.• There is fine tremors when examined on outstretch hands but there is no flapping

tremors.• (note: palmar erythema and a course flapping tremor , Warm hands with dilated veins , bounding

pulses ,are signs of of CO2 retention. And a fine tremor is associated with beta 2 agonist use. Also look for other points like, wasting of the small muscles of the hand (Pancoast tumour) and nicotine stains.• Pain and/or swelling of hands/wrists suggesting possible hypertrophic pulmonary

osteoarthropathy.)

COPD on AE

• The goal of treatment in COPD AE is minimize the impact of current exacerbation and to prevent the development of subsequent exacerbations.

Signs of Severity

Exacerbation of COPD

• The Global Initiative for COPD(GOLD), a report produced by the National Heart, Lung, and Blood Institute (NHLBI) and the WHO, defines an exacerbation of COPD as an acute increase in symptoms beyond normal day-to-day variation. This generally includes an acute increase in one or more of the following cardinal symptoms:

1. Cough increases in frequency and severity2. Sputum production increases in volume and/or changes character3. Dyspnea increases

Common bacteria are;

• Haemophilus influenzae• Moraxella catarrhalis• Streptococcus pneumoniae• Pseudomonas aeruginosa• Enterobacteriaceae• Haemophilus parainfluenzae• Staphylococcus aureus(Note: Despite the frequent implication of bacterial infection, chronic suppressive or "rotating" antibiotics are not beneficial in patients with COPD and is not recommended.)

Most common cause is viral upper RTI

Criteria for hospitalization

American Thoracic Society/European Respiratory Society (ATS/ERS) • Inadequate response of symptoms to outpatient management• Marked increase in dyspnea• Inability to eat or sleep due to symptoms• Worsening hypoxemia• Worsening hypercapnia• Changes in mental status• Inability to care for oneself (ie, lack of home support)• Uncertain diagnosis• High risk comorbidities including pneumonia, cardiac arrhythmia, heart

failure, diabetes mellitus, renal failure, or liver failure

• In addition, there is general consensus that acute respiratory acidosis justifies hospitalization.

Bronchodilators

•Typically, patients are treated with an inhaled b-agonist, often with the addition of an anticholinergic agent.

•Patients are often treated initially with nebulized therapy, as such treatment is often easier to administer in older patients or to those in respiratory distress.

Antibiotics• Inexpensive common oral antibiotics usually adequate .Broader

spectrum if not responsive.Glucocorticoids• Among patients admitted to the hospital, the use of glucocorticoids

has been demonstrated to reduce the length of stay, hasten recovery, 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.

Oxygen

• Target Pao2: 60-70 mmhg• Nasal cannulae can provide flow rates up to 6 L /min

with an associated FiO2 of approximately 40 % • Simple facemasks can provide an FiO2 up to 55 %

using flow rates of 6 to 10 L per minute. • Venturi masks can deliver an FiO2 of 24, 28, 31, 35,

40, or 60 percent.• Non-rebreathing masks with a reservoir, one-way

valves, and a tight face seal can deliver an inspired oxygen concentration up to 90 %.

Noninvasive Mechanical Ventilatory Support

Contraindications to NIPPV

• cardiovascular instability, • impaired mental status or inability to cooperate, • copious secretions or the inability to clear secretions, • craniofacial abnormalities • extreme obesity, • or significant burns.

Causes of Chronic cough

A chronic cough is usually defined as a cough that lasts for eight weeks or longer.

ECG changes in COPD

• P pulmonale (right atrial enlargement)• Low voltage QRS• Right axis deviation• Right bundle branch block (usually due to RVH)• Poor progression of R waves in precordial leads

References

1. Global strategy for the diagnosis, management, and prevention of copd . Updated 2014

2. Harrison's Principles of Internal medicine .18th edition

3. Davidson's Principles and practice of Medicine .21st edition.

4. Uptodate version 20.35. Mercksmannual