Chronic Obstructive Pulmonary Disease (COPD)

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU

Pathogenesis

Epigenetic determinants activate or silence fetal genes through alterations in DNA, histone methylation and acetylation.


DNA associates with histone proteins to form chromatin. Image source: Wikipedia, GNU Free Documentation License.

Histones are the chief protein components of chromatin. They act as spools around which DNA winds, and they play a role in gene regulation. Without histones, the unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA, but wound on the histones it has about 90 millimeters of chromatin.

Histone acetylation opens the chromatin to allow transcription of DNA. Histone deacetylation decreases gene expression. Deacetylation is reduced in chronic obstructive pulmonary disease (COPD).


T cell predominance in lung diseases:

CD8: hypersensitivity pneumonitis (HP) and COPD
Th2, CD4: Asthma, ABPA, pulmonary eosinophilia
Th1, CD4: granulomatous TB, sarcoid, berylliosis

Lower Airway Changes in Asthma and COPD

Cellular infiltrate: CD4 in asthma vs. CD8 in COPD.

Epidemiology

1 in 4 individuals will develop COPD during their lifetime (Lancet, 2011). 25% of persons in the U.S. smoke cigarettes, down from 40% in the 1960s.

Not all smokers develop COPD. Only 15-20% of smokers have airflow obstruction (COPD). Obstruction is defined as a ratio of FEV1 to forced vital capacity (FVC) less than 0.65.


Mind map of Chronic Obstructive Pulmonary Disease (COPD) (click to enlarge the image).

Diagnosis

- History
- CXR - nonspecific
- CT chest -- bullae

Stages of COPD

Global Initiative for Chronic Obstructive Lung Disease (GOLD) has developed a staging system for COPD. Staging systems for asthma, COPD and allergic rhinitis all use similar categories - MMS: mild, moderate and severe.

COPD stages:
- Stage 0, chronic cough and sputum and normal PFTs
- Mild, FEV1 higher than 80% of predicted
- Moderate, FEV1 50-79% of predicted
- Severe, FEV1 30-49% of predicted

Pathogenesis

Chronic inflammation leads to remodeling, collagen deposition, and consequently, irreversible airways obstruction. Young adults with COPD should be screened for A1AT deficiency - 2% of adults with COPD have A1AT deficiency.

Treatment of COPD

Mnemonic for treatment modalities in COPD: B CAOS

Bronchodilators

Corticosteroids
Antibiotics and Vaccinations
Oxygen
Smoking cessation

Bronchodilators

Bronchodilators are the mainstay of COPD treatment. Ipratropium and albuterol are preferred. Theophylline has limited use due to potential toxicity, frequent medication interactions, and need to monitor blood levels.

Tiotropium (Spiriva) is a long acting muscarinic antagonist (anticholinergics) that decreases frequency of COPD exacerbations, especially when combined with a LABA and inhaled steroid.

Tiotropium (18 µg inhaled once daily, HandiHaler) was significantly more effective than 40 µg ipratropium 4 times daily in improving lung function over a 13 week period. These data support the use of tiotropium as first line treatment for the long term maintenance treatment of patients with COPD.

A randomized, double-blind trial of 4 years of therapy with tiotropium or placebo in 5993 adults with COPD, showed that tiotropium was associated with improvements in lung function, quality of life, and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV1.

Myocardial infarction developed in 67 patients in the tiotropium group and 85 in the placebo group (relative risk, 0.73) and stroke developed in 82 in the tiotropium group and 80 in the placebo group (relative risk, 0.95).

The accompanying editorial in NEJM noted that COPD, similarly to asthma, is a heterogenous disease or even, a group of diseases. "COPD in the singular is probably a misnomer. It is more appropriate to view COPD as a syndrome that encompasses a variety of obstructive diseases that share a common exposure but differ in terms of mechanism of disease and response to therapy."

Corticosteroids

Antibiotics and Vaccinations

Up to 78% of COPD exacerbations are due to bacterial infections, viral infections, or both (Lancet, 2012). An empiric course of antibiotics is recommended for COPD exacerbations when there is increased sputum production or purulent sputum. Antibiotics should cover the most common pathogens in COPD exacerbation: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Long-term antibiotic suppression is not beneficial.

Influenza vaccination reduces mortality by 50%.

Supplemental Oxygen

Home O2 therapy for more than 15 hours/day for chronic hypoxemia prolongs survival in COPD. Nocturnal oxygen is less beneficial.

Smoking Cessation

Smoking directly causes more than 430,000 deaths each year. 25% of American adults smoke (50 million people). 70% have made at least one attempt to quit, 46% make an annual attempt.

Smoking during adolescence causes genetic changes that lead to lung cancer later in life, even a person had stopped smoking. People who had never smoked lived an average of 10 years longer than heavy smokers (defined as more than 20 cigarettes per day) in a Finnish study.

Involuntary smoking is the third most common preventable cause of death.

Physicians fail to discuss smoking cessation during 50% of patient visits. Physician’s advice increases the rates of smoking cessation by about 30%, particularly if a 3-4-minute counseling session is provided.

The average annual rate of decline in FEV1 is 20 to 30 mL in normal persons and double that (50 to 60 mL) in smokers with COPD. Smoking cessation delays decline in FEV1 to near normal levels. Stopping smoking is the most effective method to prevent progression of COPD.

Telling smokers their spirometry "lung age" improves quit rates at 12 months from 6.4% to 13.6% according to a study of 561 UK smokers. The "lung age" concept (the age of the average person who has an FEV1 equal to the patient) was developed in 1985 to help patients understand complex PFTs and to show how they are prematurely aged by smoking.

Unaware of the UK study, the 2007 U.S. Preventive Services Task Force guidelines recommended against screening for COPD using spirometry.

Nicotine Patches and Gum Found were found ineffective Over the Long Term, according to Journal Watch, 2012.

References

Management of chronic obstructive pulmonary disease: Moving beyond the asthma algorithm. JACI, Volume 124, Issue 5, Pages 873-880 (November 2009).
Allergy and Immunology MKSAP, 3rd edition.
Effect on smoking quit rate of telling patients their lung age: the Step2quit randomised controlled trial. BMJ, doi:10.1136/bmj.39503.582396.25 (published 6 March 2008).
Screening for Chronic Obstructive Pulmonary Disease Using Spirometry: Summary of the Evidence for the U.S. Preventive Services Task Force. Annals of Int Med, 1 April 2008 | Volume 148 Issue 7.
A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease. Donald P. Tashkin, M.D., Bartolome Celli, M.D., Stephen Senn, Ph.D., Deborah Burkhart, B.S.N., Steven Kesten, M.D., Shailendra Menjoge, Ph.D., Marc Decramer, M.D., Ph.D., for the UPLIFT Study Investigators. NEJM, 10/2008.
COPD and Declining FEV1 — Time to Divide and Conquer? John J. Reilly, M.D. NEJM, 10/2008.
A randomised controlled comparison of tiotropium and ipratropium in the treatment of chronic obstructive pulmonary disease. J A van Noorda, Th A Bantjeb, M E Elandc, L Korduckid, P J G Cornelissend, on behalf of the Dutch Tiotropium Study Group. Thorax 2000;55:289-294 (April).
Immunologic Aspects of Chronic Obstructive Pulmonary Disease. Manuel G. Cosio, M.D., Marina Saetta, M.D., and Alvar Agusti, M.D. NEJM, Volume 360:2445-2454 June 4, 2009 Number 23.
Contemporary Management of Acute Exacerbations of COPD. A Systematic Review and Metaanalysis. Bradley S. Quon, MD, Wen Qi Gan, MD, and Don D. Sin, MD, FCCP. CHEST March 2008 vol. 133 no. 3 756-766.

Audio/Video

Chronic Obstructive Pulmonary Disease (COPD). BBC Check Up, 03/2008.
Video: Dr. Cherry Wongtrakool Discusses Interpretation of Spirometry Values in Obstructive
Lung Disease. InsiderMedicine, 03/2008.
Understanding Chronic Obstructive Pulmonary Disease. Illumistream, YouTube.

Related Reading

COPD: An update for the primary physician from CCJM 2014 http://buff.ly/1mXuSgR
Desperate to Cry, Desperate Not To. NYTimes.
Outpatient Management of Severe COPD. NEJM Review, 2010.
'Frequent Exacerbation' Type of COPD Proposed http://goo.gl/QhbI
Frequent exacerbations in COPD: What to do? BMJ 10-minute consultation, 2011.
Action plan is a key component of self-management programs in patients with COPD. Thorax, 2011.
COPD discharge care bundle - a short list of evidence-based practices to be implemented prior to discharge. Thorax, 2011.
Urinary desmosine levels are raised by exacerbations of COPD. Thorax, 2012.

Published: 02/08/2008
Updated: 04/03/2012

2 comments:

Digitaldoc, MD said...

Good one - A better mnemonic that I use for Acute COPD - A COPD

A - AntiBiotics
C - Corticosteroids + Cigarette Cessation
O - O2 Rx
P - Pneumovax / flu shot + Phlegm Control if needed (Mucolytics)
D - Dilators

- Digitaldoc, MD
http://www.usmletomd.com/smartmd/2006/04/copd-treatment.html

Anonymous said...

Mnemonic by Digitaldoc, MD,

A good one. I like it.